case study on osteoporosis

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• v.14(4); 2022 Apr

Osteoporosis: A Step-by-Step Case-Based Study

Lokesh goyal.

1 Family Medicine, Christus Spohn, Corpus Christi, USA

Kunal Ajmera

2 Epidemiology and Public Health, Calvert Health Medical Center, Prince Frederick, USA

Osteoporosis is a common disease that affects our elderly population. This disease usually gets undiagnosed for an extended period. Osteoporosis increases the risk of fracture in our elderly population and increases morbidity. The cost associated with osteoporosis does carry a substantial burden in our society. Here, we present a case of osteoporosis with a fracture diagnosed in clinical settings. We discuss different etiology, pathophysiology, and treatment options available to treat this medical condition.

Introduction

Osteoporosis is a disease that causes a decrease in bone mass, increasing bone fragility and fracture [ 1 ]. Osteoporosis is a common disease, and it impacts one in three post-menopausal women and one in five men worldwide. There are roughly 200 million men and women who have osteoporosis in this world. The cost and morbidity associated with osteoporosis carry a substantial burden in our society. According to World Health Organization (WHO), a patient is diagnosed with osteoporosis if the Bone Mineral Density (BMD) T-score = -2.5 [ 1 - 3 ]. The test used to calculate the T score is also called the DXA scan. There are many instruments currently available that calculate the risk of fracture, one of them is called the Fracture risk algorithm (FRAX). FRAX calculates the risk of significant fractures (in ten years) like vertebral and hip fractures due to osteoporosis. FRAX can look at data provided by DXA and use it to predict the risk of fractures more accurately. In this case, we will focus on a patient who has osteoporosis. We will focus on etiology, pathophysiology and treatment options as well.

Case presentation

Patient X is a 62-year-old Caucasian female who presents to the outpatient clinic with right wrist pain and swelling following a fall on an outstretched hand in the garage at home. This patient has a past medical history of hypertension (HTN), chronic heart failure (CHF), pneumonia, chronic obstructive pulmonary disease (COPD), asthma, gastric ulcer, menopause (age 50), stooped posture, and vertebral bone fracture. The patient has a family history of CHF and HTN in her brother (age 55), a pelvic fracture in her mother (age 82), and the mother was also diagnosed with osteoporosis. The patient’s father has HTN. Patient X is married with four children and works in Walmart. She smokes one pack of cigarettes every day and occasionally drinks alcohol. She does no exercise and is fully mobile with no disabilities. The patient does not report symptoms of orthopnea, weakness, chest pain, palpitation, paroxysmal nocturnal dyspnea, or excessive bleeding. The patient is currently taking lisinopril for decreasing afterload; furosemide for reducing edema; atorvastatin for hypercholesterolemia; metoprolol for decreasing heart rate; omeprazole for stomach acidity; fluticasone for her asthma, and epidural steroid injection for lower back pain. Patient X reports to the clinic in acute distress and is oriented to time, person and place. The patient weighs 250 lbs., BP 145/88, pulse 90, and O 2 saturation level of 92%. The patient lungs were clear on auscultation bilaterally. The cardiovascular exam showed a regular rate and rhythm without any murmurs. The right wrist is swollen and hurts to move. There was no edema on the left hand or feet. Radial, femoral, and dorsal pedis pulses were normal bilaterally. The patient was sent to the hospital to get an X-ray of the right hand (Figure ​ (Figure1), 1 ), which revealed Colle’s fracture (distal radius) on the right hand. The hospital then puts a cast on the patient’s hand. The blood test was normal in this patient except for low levels of Vitamin D. The patient was also asked to get a DEXA scan, which revealed a T score of -2.9 (less than -2.5 is osteoporosis). The patient was started on bisphosphonates, raloxifene (selective estrogen receptor modulator [SERM]), and also given Vitamin D (1,000 mg) and calcium tablets. The patient was advised to start exercising daily and eat a healthy diet. She was also asked to be careful while walking.

Pathophysiology

The cause of osteoporosis [ 1 - 3 ] is an imbalance between bone formation and bone reabsorption. A typical bone is constantly being broken down and reformed. Around 10% of our total bone mass is under constant remodeling at any given time [ 4 ]. Due to menopause [ 5 , 6 ], the amount of estrogen secreted in a woman can decline rapidly [ 5 , 7 ]. The lack of estrogen [ 8 ] will increase the risk of bone reabsorption and decrease the deposition of new bone. Due to menopause, we also see an increase in basic multicellular units made of osteoclasts and osteoblasts cells. These osteoclast and osteoblast cells will sequentially resorb old bone and form new bone. This prolongs the osteoclast resorption time and relative shortening of the time for osteoblastic bone formation. The recent studies [ 6 , 9 , 10 ], both done in vitro and in vivo, show that, in the eugonadal state, estrogen will inhibit receptor activators of nuclear factor-κ B ligand (RANKL). RANKL [ 9 , 10 ] is a molecule found on the bone marrow stromal cells/osteoblast precursors and T and B cells. A decrease in the concentration of Vitamin D can also increase the risk of fracture and lower the BMD in the patient’s body. The primary source of Vitamin D comes from sunlight and diet. A severe deficiency of Vitamin D levels can lead to osteomalacia (in adults) or rickets (in children). These diseases cause softening of bones and increase the risk of fracture tremendously. The use of anti-acidity medications [ 2 ] like proton pump inhibitors (PPI) or H2 receptor blockers (Cimetidine) has been shown to increase fracture risk in adults. The increase in the risk of fracture due to anti-acidity medication is that these medications induce hypochlorhydria in the human body. This hypochlorhydria affects the absorption of calcium and therefore leads to a decrease in calcium in the body, increasing the risk of fracture. Any changes in sex hormones [ 8 ] are the most critical factor which affects bone loss due to aging; however, we still need to recognize the non-sex steroid hormonal changes that also occur in the human body. The most important hormone that affects bone physiology is the decrease in growth hormone secretion (as we age) from the pituitary gland. This decrease in growth hormone leads to a decrease in the production of insulin-like growth factors (IGF-1 and IGF-2) [ 4 - 6 ] from the liver. These hormones have a role in osteoblast activity and differentiation. A decrease in IGF is also associated with increased IGF inhibitory binding protein (IGFBP-2). An increase in IGFBP-2 in the human body leads to a decrease in BMD in adults [ 6 - 8 ].

The most pivotal step in the diagnosis of osteoporosis is a DEXA scan (dual-energy x-ray absorptiometry). This test measures BMD. T score of less than -2.5 is considered a diagnosis of osteoporosis. Whereas a score of -1 to -2.5 is considered osteopenia. The NOF guidelines [ 4 - 6 ] state that a patient should undergo osteoporosis treatment not just after a hip/vertebral fracture or with a T- score≤−2.5, but treatment should also be considered in postmenopausal women and men with osteopenia (age > 50). The main goal of osteoporosis treatment is not just to increase BMD but also to prevent fractures in the future. Calcium and Vitamin D deficiency leads to an increase in the risk of bone loss and muscle weakness. This deficiency will, in turn, increase the patient’s risk of falling and fracture. By prescribing calcium and Vitamin D supplements to the patient, we can decrease fracture risk by 10%-15%. Multiple outcomes of the raloxifene evaluation (MORE) [ 6 , 7 ] study has shown that raloxifene, a SERM, reduces the risk of vertebral fracture by 30% if used continuously for three years. National Institute of Health and Care Excellence (NICE) [ 6 , 7 ] recommends using raloxifene in postmenopausal women at increased risk for osteoporosis or women intolerant of Bisphosphonates. Bisphosphonate is the class of drugs used for preventing osteoporosis. It has been the best choice for the treatment of osteoporosis since the 1960s. Bisphosphonates and their analogs bind at sites where bone resorption and new bone formation occur. The osteoclasts will ingest bisphosphonates bound to the mineral and therefore inhibit the function of osteoclasts. This will consequently lead to inhibition of bone resorption.

In addition to her past medical history and family history, these findings put this patient at risk of fracture due to osteoporosis. The past medical history of patient X (menopause, steroid meds, and old age) is consistent with the common risk factors for the development of osteoporosis. Patient X also has a history of vertebral fracture, which is most likely to have been caused due to osteoporosis. The most pertinent physical exam findings for this patient are the presence of stooped posture, history of vertebral fracture, and chronic back pain. The most critical risk factor for fracture in the case of osteoporotic patients is an unstable gait, which increases the risk of falls and, therefore, fractures. To rule out any risk of future fractures, this patient went through a thorough examination (gait abnormalities, orthostatic hypotension, and cognitive impairment). Patient X also went through a thorough neurological examination to rule out any spinal cord or peripheral nerves being compromised. This patient was prescribed bisphosphonates and calcitonin, which will help in inhibiting the osteoclast function. Raloxifene (SERM), this drug, will help decrease the risk of vertebral fractures and breast cancer in women. Vitamin D and Calcium supplements will help in increasing the BMD in the bones and decrease the risk of osteoporosis. The patient was also asked to have a good diet and exercise daily to encourage weight loss. The patient must do some weight-bearing exercise as this helps increase the BMD and helps decrease osteoporosis. Due to an increase in fracture risk from falling, the patient was advised to use a walker while walking.

Conclusions

Through this case presentation, we realize that patients in our society are not appropriately screened for osteoporosis during their lifetime. This is usually due to a lack of medical knowledge among our patient population and sometimes the cost as well. Osteoporosis remains a public health problem and an economic burden to our society. As the incidence of osteoporosis continues to increase, it is clear that preventive interventions must be considered early on and sometimes as early as in utero. Patient education in primary care should focus on the benefits of a healthy lifestyle, a nutritious, and balanced diet (with Vitamin D and calcium supplements) in preventing the risk of osteoporosis. Patients must also avoid smoking, drinking, and illicit drugs as they have been shown to decrease the BMD and increase the risk of osteoporosis.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The authors have declared that no competing interests exist.

Human Ethics

Consent was obtained or waived by all participants in this study

Ohio State nav bar

The Ohio State University

• BuckeyeLink
• Find People
• Search Ohio State

Patient Case Presentation

Ms. C.S. is a 46-year-old white female, who presents to her primary care physician for further work up after being seen and treated by an orthopedic surgeon for a right distal radius fracture. Patient sustained a low impact fall from standing which led to her injury. She states generally she doesn’t have pain but rates pain in wrist seven out of ten on pain scale.

Pertinent Past Medical and Surgical History

Jones, R. (2013). Distal radius [Picture]. Retrieved from https://emrems.com/2013/10/02/distal-radius/

• Bipolar disorder, diagnosed age 23, medically treated with lithium and cognitive behavior therapy
• Hysterectomy, age 44
• Diabetes type 1, diagnosed age 2
• Depression, diagnosed age 17

Pertinent Social History

• One pack per day smoker since age 17
• Newly divorced after 25 years of marriage
• Height 5’2 weight 85 pounds

Pertinent Family History

• Father alive at age 76 with history of bipolar disorder
• Mother died of cardiac arrest after a myocardial infarction 60 days post hip replacement at age 66
• Brother alive at age 50 with history of hyperthyroidism
• Sister alive at age 52 with no pertinent medical history

Talk to a specialist nurse

0808 800 0035

• Newly diagnosed
• Signs and symptoms
• Scans, tests and results
• Drug treatments
• Living with osteoporosis
• Spinal fractures
• Exercise and physical activity for osteoporosis
• Coronavirus
• Osteoporosis risk checker
• Bone health checklist
• Nutrition for bones
• Exercise for bones
• How to build up exercise for your bone strength
• Fact sheets, booklets and films
• Support in your area
• Free osteoporosis Helpline
• Bone Matters
• Useful organisations
• Sign up to ROS News
• Become a member
• Member log in
• Share your story
• Campaign with us
• Partner with us
• Make a donation
• Winter appeal
• Leave a gift in your will
• Play the weekly lottery
• Give in memory
• Give in celebration
• Our promise to you
• Osteoporosis conference
• National training scheme for bone densitometry
• Bone densitometry foundation course
• Fracture prevention practitioner training
• RCGP Osteoporosis eLearning
• Osteoporosis resources for primary care
• Videocasts and webinars library
• Access e-learning
• Clinical quality toolkits
• DXA quality toolkit
• Hip fracture toolkit
• Vertebral fracture toolkit
• FLS implementation toolkit
• Clinical publications and resources
• For your patients
• Healthcare sector news
• Subscribe to updates
• Networks for you
• Our current research strategy
• Our research roadmap
• Our current research projects
• Funding and support for researchers
• Get involved in research
• Animals in research policy
• How we help
• Our latest news
• Media centre
• Work with us
• Our shared beliefs
• Get in touch

Case studies

We have a diverse pool of individuals from all over the UK who have a connection with osteoporosis and have shared their story with us. If you’re looking for a personal story, please contact our media team.

Hilary's story*

"In summer 2021 I was on a camping trip with some friends when I tripped over a tent rope onto the grass. This was a relatively minor fall so I was pretty shocked to find out when I went to the hospital that I hadn't only broken my hip, but shattered my pelvis as well. I quickly had surgery for this and returned home with support from a carer. After conducting my own researching and prompting the doctor for a DXA scan, I later found out I had osteoporosis.

"I couldn't believe it when I found out that one in two post menopausal women have osteoporosis and thought 'why does nobody know about this?'. I felt frustrated that I could have been taking calcium and vitamin D to protect my bones but had no idea about this. That was really the trigger for me. I wanted to do something about it, which inspired me to share my story.

"It’s extraordinary to me that people my age, however fit or unfit they are, whatever their lifestyle could be suffering with this without even knowing and I want to share my story in the hope of raising awareness with as many people as possible."

* Please note that Hilary's story is a sample one. If you are looking for a case study to use in your work, please contact our media team.

Ed's story*

"I was diagnosed with osteoporosis at 22 years old, following a diagnosis of Coeliac disease, a condition that can increase your risk of developing osteoporosis. When the results came back, I was surprised to discover my bone density was really low and I had osteoporosis.

"My life isn't dramatically different from anyone else my age, but I do have to be slightly more cautious when taking part in activities that could lead to broken bones, such as ice skating or skiing, and I avoid certain bending and twisting movements when exercising.

"I wanted to share my story to raise awareness of the importance of bone health. I feel there isn't much representation for people my age with the condition and I want people to know that osteoporosis can impact younger people, and it doesn't mean you’re going to suddenly break in half. I think it’s important, especially for younger people, to be aware of their bone health, as by just making a few small changes in our lives we can help strengthen our bones and reduce the risk of osteoporosis."

* Please note that Ed's story is a sample one. If you are looking for a case study to use in your work, please contact our media team.

We’d like to thank all of our case studies for helping us spread awareness of osteoporosis and bone health.

If you’re living with osteoporosis, know someone with the condition, or are volunteering or fundraising for the charity, we'd love to hear about your experiences. Please contact [email protected]  to find out more.

Contact information

To speak to a case study, please contact our media team

01761 473 201

[email protected]

Help our specialist nurses continue to support those in need

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• My Account Login
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Open access
• Published: 12 April 2024

The association between body mass index and osteoporosis in a Taiwanese population: a cross-sectional and longitudinal study

• Chao-Tse Chiu 1 , 2 ,
• Jia-In Lee 3 ,
• Cheng-Chang Lu 1 , 2 ,
• Shu-Pin Huang 4 , 5 , 6 , 7 , 8 , 9 ,
• Szu-Chia Chen 7 , 10 , 11 , 12 &
• Jiun-Hung Geng 4 , 5 , 6 , 7 , 13  

Scientific Reports volume  14 , Article number:  8509 ( 2024 ) Cite this article

140 Accesses

Metrics details

• Malnutrition
• Risk factors

This study investigates the correlation between body mass index (BMI) and osteoporosis utilizing data from the Taiwan Biobank. Initially, a comprehensive analysis of 119,009 participants enrolled from 2008 to 2019 was conducted to assess the association between BMI and osteoporosis prevalence. Subsequently, a longitudinal cohort of 24,507 participants, initially free from osteoporosis, underwent regular follow-ups every 2–4 years to analyze the risk of osteoporosis development, which was a subset of the main cohort. Participants were categorized into four BMI groups: underweight (BMI < 18.5 kg/m 2 ), normal weight (18.5 kg/m 2  ≤ BMI < 24 kg/m 2 ), overweight (24 kg/m 2  ≤ BMI < 27 kg/m 2 ), and obese groups (BMI ≥ 27 kg/m 2 ). A T-score ≤ − 2.5 standard deviations below that of a young adult was defined as osteoporosis. Overall, 556 (14.1%), 5332 (9.1%), 2600 (8.1%) and 1620 (6.7%) of the participants in the underweight, normal weight, overweight and obese groups, respectively, had osteoporosis. A higher prevalence of osteoporosis was noted in the underweight group compared with the normal weight group (odds ratio [OR], 2.20; 95% confidence interval [95% CI], 1.99 to 2.43; p value < 0.001) in multivariable binary logistic regression analysis. Furthermore, in the longitudinal cohort during a mean follow-up of 47 months, incident osteoporosis was found in 61 (9%), 881 (7.2%), 401 (5.8%) and 213 (4.6%) participants in the underweight, normal weight, overweight and obese groups, respectively. Multivariable Cox proportional hazards analysis revealed that the risk of incident osteoporosis was higher in the underweight group than in the normal weight group (hazard ratio [HR], 1.63; 95% CI 1.26 to 2.12; p value < 0.001). Our results suggest that BMI is associated with both the prevalence and the incidence of osteoporosis. In addition, underweight is an independent risk factor for developing osteoporosis. These findings highlight the importance of maintaining normal weight for optimal bone health.

Similar content being viewed by others

Association between body fat and bone mineral density in Korean adults: a cohort study

Hyunjung Yoon, Eunju Sung, … Sujeong Shin

Trends in osteoporosis and mean bone density among type 2 diabetes patients in the US from 2005 to 2014

Yingke Xu & Qing Wu

Underweight and risk of fractures in adults over 40 years using the nationwide claims database

Sang-Min Park, Jiwon Park, … Jin S. Yeom

Introduction

Osteoporosis, a pervasive bone metabolic disorder characterized by diminished bone mineral density (BMD) and compromised bone microarchitecture, poses a formidable challenge to global public health 1 . The disorder results in skeletal fragility and significantly elevates the risk of fractures and consequently the burden of morbidity and mortality, particularly concerning hip fractures in older age 2 . The determinants of osteoporosis are multifaceted and can be categorized into two principal domains: nonmodifiable and modifiable factors. Nonmodifiable factors encompass genetic variations, advanced age, ethnicity, sex, reproductive status, and chronic estrogen deprivation, and underlie the complexity of the etiology of osteoporosis 3 . Of these factors, advanced age and female sex are the most prominent and important risk factors for osteoporosis 4 .

In contrast to the nonmodifiable factors, modifiable factors present intriguing avenues for interventions and prevention, and include dietary habits 5 , sedentary lifestyles 6 , body composition 7 , body weight 7 , smoking 8 , prolonged corticosteroid therapy 9 , excessive alcohol 10 , coffee consumption 11 , and Vitamin D deficiency 12 . Among these factors, the interaction between body weight and bone mass plays a crucial role in bone health 7 . Mechanical loading due to body weight is an important element of this relationship, and underscores the importance of weight-bearing exercises and activities. Previous research has provided compelling evidence demonstrating that obesity and weight gain are positively correlated with higher BMD and less bone loss 13 , 14 . Conversely, thinness and weight loss are associated with lower BMD and an higher rate of bone loss, further emphasizing the critical role of body weight in skeletal health 13 , 14 .

Despite advances in our understanding of osteoporosis 14 , 15 , a significant research gap remains, particularly in the context of large-scale epidemiological studies in Asian populations. Specifically, the relationship between body mass index (BMI) and osteoporosis in Asian populations remains insufficiently explored. To address this knowledge gap, the aim of this study was to examine the nuanced connections between BMI and osteoporosis using a comprehensive dataset provided by the Taiwan Biobank (TWB), a robust population-based repository.

Materials and methods

Study participants and ethics statement.

We recruited participants from the TWB dataset, a comprehensive population-based biobank in Taiwan, which aimed at collecting and storing biological samples, along with associated health and lifestyle data, from a diverse population in Taiwan. It serves as a valuable resource for researchers studying various aspects of health and disease, including genetics, environmental influences, and lifestyle factors. The biobank facilitates investigations into the relationships between environmental exposures, and the development of diseases, with the ultimate goal of advancing medical research, improving healthcare outcomes, and facilitating personalized medicine initiatives. The objectives, methodology, and detailed information of the TWB have been documented previously 16 , 17 , 18 , 19 . BMI and BMD data were available for most of the participants, enabling us to investigate the relationship between BMI and osteoporosis. Initially, a cohort of 122,068 participants enrolled in the TWB from 2008 to 2019, as illustrated in Fig.  1 . After excluding individuals with missing data (n = 3059), the final analysis encompassed 119,009 subjects.

Study participants were classified by body mass index.

Subsequently, a longitudinal cohort of 24,507 participants, initially free from osteoporosis, underwent regular follow-ups every 2–4 years to analyze the risk of osteoporosis development, which was a subset of the main cohort (Fig.  1 ). As shown in Fig.  1 , within the TWB database, 26,921 participants underwent routine follow-up examinations, with those initially diagnosed with osteoporosis (n = 2414) excluded, resulting in 24,507 individuals included in the final analysis. Spanning from 2008 to 2019, these participants underwent regular follow-ups, completed periodic questionnaires, and underwent BMD assessments every 2–4 years.

This study received ethical approval from the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20210058). All researchers adhered to the principles outlined in the Declaration of Helsinki, and written informed consent was obtained from every participant.

BMI categories

BMI categories for adults in this study adhere to the WHO classification, which categorizes individuals based on their BMI as follows 20 :

BMI < 18.5 kg/m 2 : underweight;

18.5 kg/m 2  ≤ BMI < 24 kg/m 2 : normal weight;

24 kg/m 2  ≤ BMI < 27 kg/m 2 : overweight;

BMI ≥ 27 kg/m 2 : obese.

Study outcome and definition of osteoporosis

In the cross-sectional analysis, we scrutinized the relationship between BMI and the prevalence of osteoporosis. In the longitudinal analysis, the primary end point was the development of osteoporosis. The definition of osteoporosis in this study involved measuring estimated BMD (g/cm 2 ) through calcaneus quantitative ultrasound (QUS) (Achilles InSight, GE, USA). The T-score was calculated using the formula: the individual’s BMD minus the mean BMD in young adults, divided by the standard deviation (SD) of a normal young-adult population 21 . Osteoporosis was diagnosed when the T-score was ≤ − 2.5 SD below that of young adults.

Through an extensive literature review, we identified key variables linked to the development of osteoporosis. These variables were age 3 , sex 4 , smoking habits 8 , alcohol consumption 10 , hypertension 22 , diabetes mellitus 23 , dyslipidemia 24 , anemia 25 , serum albumin level 26 , uric acid level 27 , and kidney function 28 . Demographic and lifestyle factors including age, sex, smoking status (classified as participants who had ever smoked vs. those who had never smoked), and alcohol consumption (categorized as participants who consumed > 150c.c/week for 6 months vs. non-consumers) were assessed through self-administered questionnaires. Medical history variables such as past hypertension, diabetes mellitus, and dyslipidemia were also obtained from participant responses. Interviewers were instructed to reiterate these inquiries and verify the consistency of the responses. Clinical parameters including anemia (defined as hemoglobin < 13.5 g/dl for males and < 12.5 g/dl for females), serum albumin levels, uric acid levels, and kidney function (determined through estimated glomerular filtration rate, eGFR) were evaluated through blood tests. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula: eGFR (mL/min/1.73 m 2 ) = 175 × (Serum creatinine) − 1.154  × (Age) − 0.203  × (0.742 if female) 29 .

In the longitudinal cohort study, participants underwent regular follow-ups, typically occurring within 2–4 years following the initial appointment. These follow-ups involved completing periodic questionnaires, undergoing physical examinations, providing blood samples, and undergoing BMD tests.

To ensure the effectiveness and acuracy of data, the TWB has been complemented by the development of its infrastructure. This includes obtaining international organization for standardization (ISO) certification, implementing integrated multi-center recruitment, synthesizing data/information systems, and ensuring international accessibility. Detailed information can be found in previous studies 30 , 31 .

Statistical analyses

The participants were stratified into four groups based on their BMI: underweight, normal weight, overweight, and obese. Categorical variables were represented as percentages, while continuous variables were presented as mean ± SD. One-way ANOVA was employed to compare these groups regarding continuous variables, and the Pearson χ 2 test was used for categorical variables. To assess the association between BMI and osteoporosis prevalence, multivariable binary logistic regression analyses were conducted in the cross-sectional analysis. In addition, to evaluate the association between BMI and the risk of osteoporosis development, Kaplan–Meier and Cox proportional hazard regression analyses were performed in the longitudinal cohort. The Kaplan–Meier analysis, along with a log-rank test, was employed to estimate the cumulative incidence of osteoporosis. Survival time was defined as the duration from baseline assessment to the occurrence of incident osteoporosis or until the last follow-up visit for participants who remained osteoporosis-free. Censorship was applied to individuals lost to follow-up or deceased, with their data being censored at the date of their last examination. Cox proportional hazards analyses were conducted to ascertain the independent association between BMI and the development of osteoporosis. Furthermore, to investigate the correlation between BMI and changes in BMD T-score, one-way ANOVA was applied. Statistical significance was established at p value < 0.05. All statistical analyses were performed using R version 3.6.2 (R Foundation for Statistical Computing, Vienna, Austria) and SPSS version 20.0 (IBM Corp, Armonk, NY, USA).

Baseline characteristics of the participant classified by BMI

For the cross-sectional analysis, 119,009 participants were enrolled, with a mean age of 50 ± 11 years (Table 1 ). Overall, 3% (n = 3946) of the participants were underweight, 49% (n = 58,683) were normal weight, 27% (n = 32,190) were overweight, and 21% (n = 24,190) were obese. Notably, individuals in the underweight group were generally younger, predominantly female, and had lower rates of smoking and drinking compared to the other groups. Moreover, individuals in the underweight group had decreased prevalence rates of hypertension, diabetes mellitus, and dyslipidemia, and also lower levels of serum hemoglobin, fasting glucose, triglycerides, total cholesterol, and uric acid, along with higher BMD T-scores compared to the other groups (Table 1 ).

Association between BMI and prevalent osteoporosis

Among the 119,009 participants in the cross-sectional analysis, a total of 10,108 individuals (8.5%) were diagnosed with osteoporosis. The prevalence of osteoporosis varied among the BMI groups, with 556 (14.1%) in the underweight group, 5332 (9.1%) in the normal weight group, 2600 (8.1%) in the overweight group, and 1620 (6.7%) in the obese group (Table 2 ). Univariable binary logistic analysis identified several factors associated with prevalent osteoporosis, including BMI, age, sex, smoking, drinking, history of hypertension, diabetes mellitus, dyslipidemia, serum albumin, fasting glucose, total cholesterol, triglyceride levels, and estimated glomerular filtration rate (Supplementary Table S1 ). Multivariable binary logistic analyses, adjusting for factors associated with prevalent osteoporosis identified in univariable analyses, revealed that the individuals in the underweight group had a significantly higher odds of osteoporosis compared to those in the normal weight group (odds ratio [OR], 2.20; 95% confidence interval [95% CI], 1.99 to 2.43; p value < 0.001) (Table 2 ). Conversely, the overweight and obese groups had lower odds of osteoporosis compared to the normal weight group (OR, 0.74; 95% CI 0.71 to 0.78]; p value < 0.001; and OR, 0.69; 95% CI 0.65 to 0.74; p < 0.001, respectively) (Table 2 ). These findings remained consistent in subgroup analyses stratified by age and sex (Supplementary Table S2 ).

Association of BMI with the development of osteoporosis

To further corroborate our findings within a longitudinal cohort, we enrolled 24,507 participants who lacked osteoporosis at baseline to investigate the influence of BMI on osteoporosis development. Participants were stratified into underweight (662, 3%), normal weight (12,321, 50%), overweight (6941, 28%), and obese (4583, 19%) categories (Table 3 ). During a mean follow-up period of 47 months, newly developed osteoporosis was observed in 1556 (6.3%) of all participants, 61 (9.2%) of the underweight individuals, 881 (7.2%) of the normal weight individuals, 401 (5.8%) of the overweight individuals, and 213 (4.6%) of the obese individuals (Table 4 ). Univariable analysis revealed associations between BMI, age, sex, history of hypertension, diabetes mellitus, dyslipidemia, serum albumin, fasting glucose, and total cholesterol with incident osteoporosis (Supplementary Table S3 ). Multivariable Cox proportional hazards regression analysis, adjusting for factors associated with incident osteoporosis as indicated in Supplementary Table S3 , demonstrated that the risk of developing incident osteoporosis was greater in the underweight group compared to the normal weight group (hazard ratio [HR], 1.63; 95% CI 1.26 to 2.12; p value < 0.001) (Table 4 ). Conversely, the overweight and obese groups exhibited a lower risk of developing osteoporosis compared to the normal weight group (Table 4 ). Kaplan–Meier plots demonstrated that the time to incident osteoporosis development was significantly shorter for participants in the underweight group compared to the normal weight group (Fig.  2 ).

Time to osteoporosis development was shorter in underweight participants than normal weight participants. Kaplan–Meier plot of incident osteoporosis development according to BMI groups in 24,507 participants with follow-up data. *p value < 0.001; **p value < 0.001; ***p value < 0.001.

Subjects in the underweight group had the highest decrease in BMD T-score compared to the other groups

We further examined differences between BMI groups and changes in BMD T-score. The ΔBMD T-scores were − 0.463 ± 1.0874, − 0.338 ± 0.9831, − 0.286 ± 0.9249, and − 0.257 ± 1.0133 in the underweight, normal weight, overweight, and obese groups, respectively. The underweight group had the highest decrease in BMD T-score compared to the other groups, and this decrease was significant when compared with the normal weight group (p value = 0.008) (Table 5 ).

In this large-scale, population-based study, the underweight individuals exhibited an increased risk of osteoporosis after adjusting for confounding factors compared to the other weight groups. Moreover, they had the most significant decrease in BMD T-score compared to the other groups over a mean follow-up period of 47 months. To the best of our knowledge, this is the largest study to demonstrate underweight status as an independent risk factor for the development of osteoporosis.

Numerous studies have demonstrated a positive relationship between BMI and BMD. For example, Walsh and colleagues reported a significant correlation between BMI and BMD, and proposed that potential mechanisms may include increased loading and heightened aromatase activity 32 . Another study conducted in the US revealed that each unit increase in BMI was linked to a 0.0082 g/cm 2 increase in BMD (p value < 0.001) 33 . In addition, Felson et al. demonstrated the protective influence of higher body weight on BMD levels across various sites, especially in weight-bearing bones 34 . Similarly, an Asian study identified positive correlations between body weight, BMI, height, and BMD at different anatomical locations (p value < 0.05) 35 . In line with these findings, we found a robust association between BMI and osteoporosis. Notably, most previous studies have been cross-sectional, whereas we conducted a large longitudinal study and provided evidence that being underweight was an independent risk factor for developing osteoporosis.

While being underweight has been correlated with a reduced risk of cardiovascular disease, a lower weight status may be harmful to health due to suboptimal nutrition and reduced muscle mass and strength 36 . Moreover, decreased mechanical loading and muscle stress on bones can potentially lead to lower peak bone mass and increased bone loss 37 . Our findings support these studies, and demonstrated a higher incidence of osteoporosis in the underweight group compared to the normal weight group. Consequently, maintaining a healthy BMI may be an important and modifiable factor in osteoporosis prevention. A study by Lee et al. reinforces this idea, in which they identified an optimal BMI range of 23.0 to 24.9 kg/m 2 to minimize the risk of osteoporosis 38 . Beyond this range, the risk of osteoporosis decreases. Conversely, a BMI below this range may increase the risk of osteoporosis.

In the present study, underweight was not only a risk factor for the development of osteoporosis, but it was also related to a significant reduction in BMD T score (ΔBMD T-score of − 0.463 ± 1.0874). Meyer et al. investigated how weight fluctuations over three decades impacted the risk of osteoporosis, and they found that individuals who lost < 5% of their body weight had a 6.2% prevalence of osteoporosis, rising to 14.1% for a 5–10% loss and 15.1% for a > 10% loss 13 . In contrast, 2.6% of those with a 5–10% weight gain had osteoporosis, compared to 0.6% of those with a > 10% gain 13 . The authors linked a low BMI to a higher risk of osteoporosis, emphasizing the pivotal role of stable weight in maintaining bone health. Their findings also underscored the impact of weight fluctuations (> 0.25 kg/year) on BMD 13 . Rapid weight loss, especially from dieting can irreversibly decrease BMD 39 , highlighting the necessity of gradual, healthy weight management for long-term bone health.

Several modifiable factors play a crucial role in promoting bone health 40 , 41 , 42 , 43 , 44 . According to Christianson et al. 40 and other studies 41 , 42 , regular weight-bearing exercise and a balanced diet with adequate calcium, vitamin D, and protein intake are essential recommendations. In addition, other studies have shown that daily tea consumption positively influences BMD in osteoporotic women, while excessive salt and coffee consumption have negative effects on BMD 43 . Regular weight-bearing exercise can not only promote bone health but also enhance balance and motor strength, reducing the risk of falls 40 . Soltani et al. found that weight loss was associated with reduced BMD at the hip, with a more significant impact than on the spine. Calorie restriction and a combination of calorie restriction and exercise have been associated with decreased hip BMD, whereas exercise training without dietary restriction has been associated with increased hip BMD 44 . Moreover, critical modifiable lifestyle factors associated with bone health and decrease fracture risk include avoiding smoking, maintaining a healthy body weight (especially BMI ≥ 20 kg/m 2 ), limiting alcohol intake, and minimizing the risk of falls at home 40 .

Two potential mechanisms have been proposed to explain how body mass affects osteoporosis. The first mechanism involves mechanical loading, where additional weight imposes higher static mechanical stress on bones 14 . This stress can then trigger adaptive responses, leading to changes in bone quality and structure 14 . Heavy individuals tend to attain higher peak BMD in early adulthood, which exerts a greater load on weight-bearing joints and results in higher BMD, reducing the likelihood of osteoporosis in old age 14 . The second mechanism involves the physiological function of adipose tissue, which influences bone through an endocrine pathway 45 , 46 , 47 . Adipose tissue impacts bone metabolism by metabolizing sex steroids, indirectly protecting against bone loss. Adipose tissue expresses and secretes adipocytokines such as leptin and adiponectin 45 , 46 , 47 . Leptin stimulates osteoblast proliferation, mineralization, collagen synthesis, and inhibits bone resorption, while adiponectin promotes excessive bone resorption associated with bone loss, negatively affecting BMD, particularly in postmenopausal women 45 , 46 . Current evidence indicates that leptin positively affects BMI, while adiponectin is negatively associated with BMD, making it a relevant adipokine negatively linked to postmenopausal osteoporosis 47 .

The strengths of this study include that it is the first large-scale, cross-sectional, and longitudinal study to explore the interconnection between BMI and osteoporosis among an Asian Han population. Utilizing a nationally representative cohort of over 120,000 Taiwanese men and women greatly enhanced the statistical power of our results. Not only did we establish a clear link between BMI and osteoporosis prevalence, but we also identified the incidence of newly developed osteoporosis. Our findings offer invaluable insights for healthcare professionals, empowering them to engage in informed discussions with patients about the impact of BMI status on bone health. Nonetheless, our study also has limitations that warrant acknowledgment. Firstly, we used calcaneal QUS to assess BMD, while previous studies have utilized dual energy X-ray absorptiometry (DXA)-derived BMD. The choice of measurement technique stems from the advantages of QUS, which is commonly used for peripheral bones such as the calcaneus. The calcaneus is primarily composed of cancellous bone with minimal soft tissues and a large measurable plane, making it ideal for QUS assessments 48 . Discrepancies between QUS and DXA measurements arise from the fundamental differences in technology and the measurement site. The calcaneus, with a lower cortical bone proportion, is subject to distinct loading mechanisms compared to the proximal femur 49 . Despite this, numerous studies have validated that calcaneal QUS is a reliable tool for assessing BMD and shown its efficiency in diagnosing osteoporosis 48 . Secondly, we did not monitor weight changes in the participants, limiting our ability to substantiate the impact of weight gain on bone loss. In addition, we did not explore correlations between BMD and other health indicators such as fat mass, lean mass, fat distribution, peripheral and visceral fat tissue, and waist circumference, all of which may influence BMD. Thirdly, although we adjusted for several covariates, some crucial confounding factors were not considered, including the use of medications affecting bone metabolism, specific hormone therapies, nutritional supplements, serum calcium levels, and dietary patterns. Other factors such as prior fractures, surgical history, and other disorders, which could have significantly impacted our correlation analyses, were also omitted. Furthermore, due to the absence of data on prior fractures, we could not assess the relationship between osteoporotic fracture risk and BMI.

Our results suggest that BMI is associated with both the prevalence and the incidence of osteoporosis. In addition, underweight is an independent risk factor for developing osteoporosis. These findings highlight the importance of maintaining normal weight for optimal bone health.

Data availability

The data underlying this study are from the Taiwan Biobank. Due to restrictions placed on the data by the Personal Information Protection Act of Taiwan, the minimal data set cannot be made publicly available. Data may be available upon request to interested researchers. Please send data requests to Szu-Chia Chen, Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University.

Salari, N. et al. Global prevalence of osteoporosis among the world older adults: A comprehensive systematic review and meta-analysis. J. Orthop. Surg. Res. 16 (1), 669. https://doi.org/10.1186/s13018-021-02821-8 (2021).

Article   PubMed   PubMed Central   Google Scholar  

Guzon-Illescas, O. et al. Mortality after osteoporotic hip fracture: Incidence, trends, and associated factors. J. Orthop. Surg. Res. 14 (1), 203. https://doi.org/10.1186/s13018-019-1226-6 (2019).

Pouresmaeili, F., Kamalidehghan, B., Kamarehei, M. & Goh, Y. M. A comprehensive overview on osteoporosis and its risk factors. Ther. Clin. Risk Manag. 14 , 2029–2049. https://doi.org/10.2147/tcrm.s138000 (2018).

Article   CAS   PubMed   PubMed Central   Google Scholar  

De Martinis, M. et al. Gender differences in osteoporosis: A single-center observational study. World J. Men’s Health. 39 (4), 750–759. https://doi.org/10.5534/wjmh.200099 (2021).

Article   Google Scholar  

Muñoz-Garach, A., García-Fontana, B. & Muñoz-Torres, M. Nutrients and dietary patterns related to osteoporosis. Nutrients. https://doi.org/10.3390/nu12071986 (2020).

Pearson, J. A., Burkhart, E., Pifalo, W. B., Palaggo-Toy, T. & Krohn, K. A lifestyle modification intervention for the treatment of osteoporosis. Am. J. Health Promot. 20 (1), 28–33. https://doi.org/10.4278/0890-1171-20.1.28 (2005).

Article   PubMed   Google Scholar  

Zhao, L. J. et al. Relationship of obesity with osteoporosis. J. Clin. Endocrinol. Metab. 92 (5), 1640–1646. https://doi.org/10.1210/jc.2006-0572 (2007).

Article   CAS   PubMed   Google Scholar  

Yoon, V., Maalouf, N. M. & Sakhaee, K. The effects of smoking on bone metabolism. Osteoporos. Int. 23 (8), 2081–2092. https://doi.org/10.1007/s00198-012-1940-y (2012).

Briot, K. & Roux, C. Glucocorticoid-induced osteoporosis. RMD Open 1 (1), e000014. https://doi.org/10.1136/rmdopen-2014-000014 (2015).

Godos, J. et al. Alcohol consumption, bone mineral density, and risk of osteoporotic fractures: A dose-response meta-analysis. Int. J. Environ. Res. Public Health. https://doi.org/10.3390/ijerph19031515 (2022).

Kim, S. Y. Coffee consumption and risk of osteoporosis. Korean J. Fam. Med. 35 (1), 1. https://doi.org/10.4082/kjfm.2014.35.1.1 (2014).

Romano, F. et al. Osteoporosis and dermatoporosis: A review on the role of vitamin D. Front. Endocrinol. 14 , 1231580. https://doi.org/10.3389/fendo.2023.1231580 (2023).

Meyer, H. E., Søgaard, A. J., Falch, J. A., Jørgensen, L. & Emaus, N. Weight change over three decades and the risk of osteoporosis in men: The Norwegian Epidemiological Osteoporosis Studies (NOREPOS). Am. J. Epidemiol. 168 (4), 454–460. https://doi.org/10.1093/aje/kwn151 (2008).

Asomaning, K., Bertone-Johnson, E. R., Nasca, P. C., Hooven, F. & Pekow, P. S. The association between body mass index and osteoporosis in patients referred for a bone mineral density examination. J. Women’s Health 15 (9), 1028–1034. https://doi.org/10.1089/jwh.2006.15.1028 (2006).

Wardlaw, G. M. Putting body weight and osteoporosis into perspective. Am. J. Clin. Nutr. 63 (3 Suppl), 433s–436s. https://doi.org/10.1093/ajcn/63.3.433 (1996).

Chen, C. H. et al. Secondhand smoke increases the risk of developing kidney stone disease. Sci. Rep. 11 (1), 17694. https://doi.org/10.1038/s41598-021-97254-y (2021).

Article   ADS   CAS   PubMed   PubMed Central   Google Scholar  

Chang, C. W. et al. Metabolic syndrome increases the risk of kidney stone disease: A cross-sectional and longitudinal cohort study. J. Pers. Med. https://doi.org/10.3390/jpm11111154 (2021).

Tang, T. Y. et al. The association between menopause, postmenopausal hormone therapy, and kidney stone disease in Taiwanese women. Ann. Epidemiol. 78 , 13–18. https://doi.org/10.1016/j.annepidem.2022.12.002 (2023).

Lee, M. R., Ke, H. L., Huang, J. C., Huang, S. P. & Geng, J. H. Obesity-related indices and its association with kidney stone disease: A cross-sectional and longitudinal cohort study. Urolithiasis. 50 (1), 55–63. https://doi.org/10.1007/s00240-021-01288-w (2022).

Weir, C. B. & Jan, A. BMI classification percentile and cut off points. StatPearls . StatPearls Publishing. Copyright © 2023. (StatPearls Publishing LLC, 2023).

Lu, Y. H. et al. Betel nut chewing decreased calcaneus ultrasound T-score in a large Taiwanese population follow-up study. Nutrients. https://doi.org/10.3390/nu13103655 (2021).

McFarlane, S. I., Muniyappa, R., Shin, J. J., Bahtiyar, G. & Sowers, J. R. Osteoporosis and cardiovascular disease: Brittle bones and boned arteries, is there a link?. Endocrine. 23 (1), 1–10. https://doi.org/10.1385/endo:23:1:01 (2004).

Leidig-Bruckner, G. & Ziegler, R. Diabetes mellitus a risk for osteoporosis?. Exp. Clin. Endocrinol. Diabetes. 109 (Suppl 2), S493–S514. https://doi.org/10.1055/s-2001-18605 (2001).

Anagnostis, P., Florentin, M., Livadas, S., Lambrinoudaki, I. & Goulis, D. G. Bone health in patients with dyslipidemias: An underestimated aspect. Int. J. Mol. Sci. https://doi.org/10.3390/ijms23031639 (2022).

Kim, S. Y., Yoo, D. M., Min, C. & Choi, H. G. Association between osteoporosis and low hemoglobin levels: A nested case-control study using a National Health Screening Cohort. Int. J. Environ. Res. Public Health. 18 (16), 8598. https://doi.org/10.3390/ijerph18168598 (2021).

D’Erasmo, E. et al. Relationship between serum albumin and bone mineral density in postmenopausal women and in patients with hypoalbuminemia. Horm. Metab. Res. 31 (6), 385–388. https://doi.org/10.1055/s-2007-978760 (1999).

Li, J. Y. et al. Hyperuricemia and its association with osteoporosis in a large Asian cohort. Nutrients. https://doi.org/10.3390/nu14112206 (2022).

Huh, J. H. et al. Lower serum creatinine is associated with low bone mineral density in subjects without overt nephropathy. PLoS ONE. 10 (7), e0133062. https://doi.org/10.1371/journal.pone.0133062 (2015).

Huang, C. Y. et al. Chronic kidney disease and its association with cataracts—A cross-sectional and longitudinal study. Front. Public Health. 7 (10), 1029962. https://doi.org/10.3389/fpubh.2022.1029962 (2022).

Lin, J. C., Hsiao, W. W. & Fan, C. T. Transformation of the Taiwan Biobank 3.0: Vertical and horizontal integration. J. Transl. Med. 18 (1), 304. https://doi.org/10.1186/s12967-020-02451-4 (2020).

Lin, J. C., Fan, C. T., Liao, C. C. & Chen, Y. S. Taiwan Biobank: Making cross-database convergence possible in the Big Data era. Gigascience. 7 (1), 1–4. https://doi.org/10.1093/gigascience/gix110 (2018).

Article   ADS   PubMed   Google Scholar  

Walsh, J. S. & Vilaca, T. Obesity, type 2 diabetes and bone in adults. Calcif. Tissue Int. 100 (5), 528–535. https://doi.org/10.1007/s00223-016-0229-0 (2017).

Lloyd, J. T. et al. Body mass index is positively associated with bone mineral density in US older adults. Arch. Osteoporos. 9 , 175. https://doi.org/10.1007/s11657-014-0175-2 (2014).

Felson, D. T., Zhang, Y., Hannan, M. T. & Anderson, J. J. Effects of weight and body mass index on bone mineral density in men and women: The Framingham study. J. Bone Mineral Res. 8 (5), 567–573. https://doi.org/10.1002/jbmr.5650080507 (1993).

Article   CAS   Google Scholar  

Wu, S. F. & Du, X. J. Body mass index may positively correlate with bone mineral density of lumbar vertebra and femoral neck in postmenopausal females. Med. Sci. Monit. 22 , 145–151. https://doi.org/10.12659/msm.895512 (2016).

Lorem, G. F., Schirmer, H. & Emaus, N. What is the impact of underweight on self-reported health trajectories and mortality rates: A cohort study. Health Qual. Life Outcomes. 15 (1), 191. https://doi.org/10.1186/s12955-017-0766-x (2017).

Coin, A. et al. Bone mineral density and body composition in underweight and normal elderly subjects. Osteoporos. Int. 11 (12), 1043–1050. https://doi.org/10.1007/s001980070026 (2000).

Lee, J. H., Kim, J. H., Hong, A. R., Kim, S. W. & Shin, C. S. Optimal body mass index for minimizing the risk for osteoporosis and type 2 diabetes. Korean J. Intern. Med. 35 (6), 1432–1442. https://doi.org/10.3904/kjim.2018.223 (2020).

Iwaniec, U. T. & Turner, R. T. Influence of body weight on bone mass, architecture and turnover. J. Endocrinol. 230 (3), R115–R130. https://doi.org/10.1530/joe-16-0089 (2016).

Christianson, M. S. & Shen, W. Osteoporosis prevention and management: Nonpharmacologic and lifestyle options. Clin. Obstet. Gynecol. 56 (4), 703–710. https://doi.org/10.1097/GRF.0b013e3182a9d15a (2013).

Hannan, M. T. et al. Effect of dietary protein on bone loss in elderly men and women: The Framingham Osteoporosis Study. J. Bone Mineral Res. 15 (12), 2504–2512. https://doi.org/10.1359/jbmr.2000.15.12.2504 (2000).

Chang, C. F., Lee, J. I., Huang, S. P., Geng, J. H. & Chen, S. C. Regular exercise decreases the risk of osteoporosis in postmenopausal women. Front. Public Health. 10 , 897363. https://doi.org/10.3389/fpubh.2022.897363 (2022).

Özpak Akkuş, Ö. & Atalay, B. Post-menopausal osteoporosis: Do body composition, nutritional habits, and physical activity affect bone mineral density?. Nutricion hospitalaria. 37 (5), 977–983. https://doi.org/10.20960/nh.03214 (2020).

Soltani, S., Hunter, G. R., Kazemi, A. & Shab-Bidar, S. The effects of weight loss approaches on bone mineral density in adults: A systematic review and meta-analysis of randomized controlled trials. Osteoporos. Int. 27 (9), 2655–2671. https://doi.org/10.1007/s00198-016-3617-4 (2016).

Głogowska-Szeląg, J., Kos-Kudła, B., Marek, B., Nowak, M. & Siemińska, L. Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis. Endokrynologia Polska. 70 (6), 478–483. https://doi.org/10.5603/EP.a2019.0043 (2019).

Jürimäe, J. & Jürimäe, T. Plasma adiponectin concentration in healthy pre- and postmenopausal women: Relationship with body composition, bone mineral, and metabolic variables. Am. J. Physiol. Endocrinol. Metab. 293 (1), E42–E47. https://doi.org/10.1152/ajpendo.00610.2006 (2007).

Shu, L., Fu, Y. & Sun, H. The association between common serum adipokines levels and postmenopausal osteoporosis: A meta-analysis. J. Cell. Mol. Med. 26 (15), 4333–4342. https://doi.org/10.1111/jcmm.17457 (2022).

Li, C., Sun, J. & Yu, L. Diagnostic value of calcaneal quantitative ultrasound in the evaluation of osteoporosis in middle-aged and elderly patients. Medicine. 101 (2), e28325. https://doi.org/10.1097/md.0000000000028325 (2022).

Weeks, B. K., Hirsch, R., Nogueira, R. C. & Beck, B. R. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children?. Bone Joint Res. 5 (11), 538–543. https://doi.org/10.1302/2046-3758.511.bjr-2016-0116.r1 (2016).

Download references

Acknowledgements

This work was supported partially by the Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and by Kaohsiung Medical University Research Center Grant (KMU-TC109A01-1)

Author information

Authors and affiliations.

Department of Orthopaedics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan

Chao-Tse Chiu & Cheng-Chang Lu

Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

Shu-Pin Huang & Jiun-Hung Geng

Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, 807, Kaohsiung, Taiwan

Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

Shu-Pin Huang, Szu-Chia Chen & Jiun-Hung Geng

Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

Shu-Pin Huang

Institute of Medical Science and Technology, College of Medicine, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospita, l, Kaohsiung Medical University, 812, Kaohsiung, Taiwan

Szu-Chia Chen

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

Department of Urology, Kaohsiung Municipal Siaogang Hospital, No. 482, Shanming Rd, Xiaogang District, Kaohsiung, 812, Taiwan

Jiun-Hung Geng

You can also search for this author in PubMed   Google Scholar

Contributions

Author Contributions: Data curation, J.-I.L. and J.-H.G.; formal analysis, Cheng-Chang Lu and J.-H.G.; investigation, S.-C.C. and J.-H.G.; methodology, Cheng-Chang Lu and J.-H.G.; project administration, J.-H.G.; resources, J.-H.G.; software, J.-H.G.; supervision, S.-C.C., S.-P H., and J.-H.G.; validation, J.-H.G.; writing—original draft, Chao-Tse Chiu and J.-H.G.; writing—review and editing, Chao-Tse Chiu and J.-H.G. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Jiun-Hung Geng .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Supplementary tables., rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Chiu, CT., Lee, JI., Lu, CC. et al. The association between body mass index and osteoporosis in a Taiwanese population: a cross-sectional and longitudinal study. Sci Rep 14 , 8509 (2024). https://doi.org/10.1038/s41598-024-59159-4

Download citation

Received : 14 January 2024

Accepted : 08 April 2024

Published : 12 April 2024

DOI : https://doi.org/10.1038/s41598-024-59159-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Epidemiologic study
• Osteoporosis
• Body mass index
• Taiwan Biobank
• Bone mineral density

By submitting a comment you agree to abide by our Terms and Community Guidelines . If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

• Publications
• Conferences & Events
• Professional Learning
• Science Standards
• Awards & Competitions
• Daily Do Lesson Plans
• Free Resources
• American Rescue Plan
• For Preservice Teachers
• NCCSTS Case Collection
• Partner Jobs in Education
• Interactive eBooks+
• Digital Catalog
• Regional Product Representatives
• e-Newsletters
• Bestselling Books
• Latest Books
• Popular Book Series
• Prospective Authors
• Web Seminars
• Exhibits & Sponsorship
• Conference Reviewers
• National Conference • Denver 24
• Leaders Institute 2024
• National Conference • New Orleans 24
• Submit a Proposal
• Latest Resources
• Professional Learning Units & Courses
• For Districts
• Online Course Providers
• Schools & Districts
• College Professors & Students
• The Standards
• Teachers and Admin
• eCYBERMISSION
• Toshiba/NSTA ExploraVision
• Junior Science & Humanities Symposium
• Teaching Awards
• Climate Change
• Earth & Space Science
• New Science Teachers
• Early Childhood
• Middle School
• High School
• Postsecondary
• Informal Education
• Journal Articles
• Lesson Plans
• e-newsletters
• Science & Children
• Science Scope
• The Science Teacher
• Journal of College Sci. Teaching
• Connected Science Learning
• NSTA Reports
• Next-Gen Navigator
• Science Update
• Teacher Tip Tuesday
• Trans. Sci. Learning

MyNSTA Community

• My Collections

Osteoporosis

Marissa, Jeremy, and Eleanor

By Lisa Marie Rubin

Share Start a Discussion

This directed case study focuses on the physiology of bone homeostasis and methods of prevention and treatment of osteoporosis. One of the overall purposes of the case is to show students that osteoporosis is not simply a disease that afflicts elderly women. Instead, students learn about Marissa, a petite 15-year-old who has just learned that her 55-year-old grandmother has osteoporosis; Jeremey, a lanky 19-year-old college sophomore who recently has become interested in weight-lifting and is thinking about using steroids to bulk up; and Eleanor, a 45-year-old woman considering hormone replacement therapy mainly to prevent osteoporosis. The case is appropriate for use in an introductory nutrition course, physiology course, pathophysiology course, or general education course focusing on the human body and disease.

Download Case

Date Posted

• Define osteoporosis and list risk factors for it.
• Describe the roles of osteoblasts and osteoclasts in bones.
• Understand basic bone physiology and the concept of peak bone mass.
• Explain how hormones (specfically, PTH, calcitonin, and estrogen) affect bone and blood calcium levels.
• Understand that bones serve as calcium reservoirs.
• Explain why calcium is vital to bone health.
• Explain how vitamin D, sodium, caffeine, and alcohol affect calcium levels in the body.
• List the best sources of calcium in addition to dairy products and calcium supplements.
• Explain how weight-bearing and/or resistance exercises protect and strengthen bones.
• Understand how long-term use of glucocorticoids can increase the risk of developing osteoporosis.
• Understand how hormone replacement therapy (HRT) can treat and/or prevent osteoporosis.
• Know the pros and cons of HRT as well as options other than HRT for the treatment of osteoporosis.

Osteoporosis; calcitonin; calcium; bone; homeostasis; hormone replacement therapy; HRT; parathyroid hormone; PTH; endocrine system

Subject Headings

EDUCATIONAL LEVEL

High school, Undergraduate lower division, General public & informal education

TOPICAL AREAS

TYPE/METHODS

Teaching Notes & Answer Key

Teaching notes.

Case teaching notes are protected and access to them is limited to paid subscribed instructors. To become a paid subscriber, purchase a subscription here .

Teaching notes are intended to help teachers select and adopt a case. They typically include a summary of the case, teaching objectives, information about the intended audience, details about how the case may be taught, and a list of references and resources.

Download Notes

Answer Keys are protected and access to them is limited to paid subscribed instructors. To become a paid subscriber, purchase a subscription here .

Download Answer Key

Materials & Media

Supplemental materials, you may also like.

Web Seminar

Join us on Thursday, June 13, 2024, from 7:00 PM to 8:00 PM ET, to learn about the science and technology of firefighting. Wildfires have become an e...

Join us on Thursday, October 10, 2024, from 7:00 to 8:00 PM ET, for a Science Update web seminar presented by NOAA about climate science and marine sa...

Secondary Pre-service Teachers! Join us on Monday, October 21, 2024, from 7:00 to 8:15 PM ET to learn about safety considerations for the science labo...

Virtual rehabilitation for patients with osteoporosis or other musculoskeletal disorders: a systematic review

Affiliations.

• 1 School of Computer Science, University of Galway, Galway, Ireland.
• 2 School of Medicine, University of Galway, Galway, Ireland.
• 3 School of Engineering, University of Galway, Galway, Ireland.
• 4 School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland.
• PMID: 38595908
• PMCID: PMC10999384
• DOI: 10.1007/s10055-024-00980-7

This study aims to identify effective ways to design virtual rehabilitation to obtain physical improvement (e.g. balance and gait) and support engagement (i.e. motivation) for people with osteoporosis or other musculoskeletal disorders. Osteoporosis is a systemic skeletal disorder and is among the most prevalent diseases globally, affecting 0.5 billion adults. Despite the fact that the number of people with osteoporosis is similar to, or greater than those diagnosed with cardiovascular disease and dementia, osteoporosis does not receive the same recognition. Worldwide, osteoporosis causes 8.9 million fractures annually; it is associated with substantial pain, suffering, disability and increased mortality. The importance of physical therapy as a rehabilitation strategy to avoid osteoporosis fracture cannot be over-emphasised. However, the main rehabilitation challenges relate to engagement and participation. The use of virtual rehabilitation to address such challenges in the delivery of physical improvement is gaining in popularity. As there currently is a paucity of literature applying virtual rehabilitation to patients with osteoporosis, the authors broadened the search parameters to include articles relating to the virtual rehabilitation of other skeletal disorders (e.g. Ankylosing spondylitis, spinal cord injury, motor rehabilitation, etc.). This systematic review initially identified 130 titles, from which 23 articles (involving 539 participants) met all eligibility and selection criteria. Four groups of devices supporting virtual rehabilitation were identified: a head-mounted display, a balance board, a camera and more specific devices. Each device supported physical improvement (i.e. balance, muscle strength and gait) post-training. This review has shown that: (a) each device allowed improvement with different degrees of immersion, (b) the technology choice is dependent on the care need and (c) virtual rehabilitation can be equivalent to and enhance conventional therapy and potentially increase the patient's engagement with physical therapy.

Keywords: Exergames; Musculoskeletal disorders; Osteoporosis; Patient engagement; VR/AR; Virtual rehabilitation for older adults.

© The Author(s) 2024.

Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass

• Original Article
• Open access
• Published: 16 April 2024

Cite this article

You have full access to this open access article

• Shanshan Lv 1 ,
• Xiang Li 1 ,
• Chong Shao 1 ,
• Ziyuan Wang 1 ,
• Yazhao Mei 1 ,
• Wendi Yang 1 ,
• Wenzhen Fu 1 ,
• Yunqiu Hu 1 ,
• Ling Sha 1 ,
• Weiwei Hu 1 ,
• Zhenlin Zhang 1 &
• Chun Wang   ORCID: orcid.org/0000-0003-4124-1575 1  

Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5 . Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient.

Low-density lipoprotein receptor-related protein 5 ( LRP5 ) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases.

Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress.

Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment.

On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up.

This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

Avoid common mistakes on your manuscript.

Introduction

Low-density lipoprotein receptor-related protein 5 (LRP5) is a type I transmembrane receptor belonging to the LDL receptor family, composed of an extracellular domain, a membrane-spanning domain, and an intracellular domain [ 1 ]. The extracellular domain is a binding region that has extremely high affinity for the ligand, composed of four YWTD β-propellers, four EGF-like domains, and LDLR type A domains [ 2 ]. It acts as a coreceptor involved in Wnt signal transduction and consequential normal osteogenic activity of osteoblasts, reported to be one of the regulators of peak bone mass in vertebrates already [ 3 ]. It is the coreceptor of Frizzled and can be activated by proteins of the Wnt family, and then through a series of intracellular reactions, β-catenin was allowed to enter the nucleus and to modulate relative gene-transcription regulators, which is the Wnt canonical pathway [ 4 ]. In the aspect of osteogenesis, it is shown to strongly activates bone formation by enhancing cell commitment toward the bone lineage and the proliferation and differentiation of osteoblasts [ 2 ]. On the other hand, Dickkopf (DKK)1 and sclerostin (SOST), the natural antagonists of the Wnt pathway, can bind Kremen and LRP5 and block this canonical pathway, leading to the inhibition of bone formation moderately and maintenance of bone homeostasis finally [ 5 ].

LRP5 has already been identified to be associated with both osteoporosis-pseudoglioma syndrome (OPPG, OMIM 259,770) and LRP5 high bone mass (LRP5-HBM, OMIM 144,750), due to LRP5 loss-of-function mutations and gain-of-function mutations, respectively [ 6 , 7 ]. The failure of properly activating Wnt signaling in osteoblasts due to loss-of-function mutations may impaired bone formation. However, the weaken binding to DKK1 and SOST because of LRP5 gain-of-function mutations reduces inhibitory effects on Wnt signaling, where osteoblast activity is increased and therefore bone formation is enhanced, which may be the cause of the high-bone-mass phenotype [ 7 , 8 ].

OPPG is an autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness [ 6 ]. Low bone mass is often found in early childhood and is usually accompanied by fragility fractures or malformations of the long bones and spine. However, some patients suffer from fractures as early as infancy [ 9 , 10 ]. And patients suffer from blindness after birth [ 6 ]. Eye problems such as phthisis bulbi, retinal detachments, and falciform folds usually appear within a few days or 1–3 years after birth [ 11 , 12 ].

In contrast, LRP5-HBM is a type of autosomal dominant bone disease, and its typical clinical characteristics of this disease include generalized high bone density; torus palatinus; and a wide, deep mandible [ 7 ]. Patients often show radiographically cortical thickening of diaphyses of long bones but usually little change of bone outer shape and dimensions, and osteosclerosis of ribs, clavicles, vertebrae, hip, metacarpals, and calvaria [ 13 ]. The most common facial changes are elongated mandible and torus palatinus, accounting for 61% and 41%, respectively [ 14 ]. Fortunately, this disease seems benign for no danger of fragile fractures and anemia, and sometimes, it is totally asymptomatic except for the imaging abnormalities [ 7 ]. However, there are some cases reported symptoms of neurological involvement such as trigeminal neuralgia, sensorineural hearing loss, partial visual field defects, mild facial paralysis, chronic occipital headache, and type I Chiari [ 15 , 16 ], speculated as the related brain tissue and nerve compression by the hyperostotic bone [ 17 ]. It is estimated that cranial nerve deficits and/or other neurological complications affect 19.4% of the patients [ 14 ]. The biochemical parameters are usually normal, including serum calcium, phosphonium, and bone turnover markers. We previously reported that two patients had elevated serum SOST levels, but the mechanism is unclear [ 18 ].

Herein, the clinical manifestations, disease-causing mutations, treatment, and follow-up of several patients were analyzed and summarized to improve the understanding of these two diseases.

Materials and methods

This protocol was approved by the Ethics Committee of the Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Written informed consents were obtained from all the subjects or their guardians. Four female and two male patients aged 6 to 64 from five families were enrolled in the present study (Fig.  1 ).

Pedigree of the two OPPG and three LRP5-HBM affected families in this study

Clinical features and biochemical and radiographic examination evaluation

Physical examination of the patients was performed, and detailed medical histories were recorded.

Biochemical parameters, including routine blood test, serum levels of calcium (Ca), phosphonium (P), alkaline phosphatase (ALP), liver and kidney functions, creatine kinase (CK) and its MB isoenzyme (CK-MB), 25-hydroxyvitamin D [25(OH)D], the intact parathyroid hormone (PTH), the bone formation marker serum osteocalcin (OC), and the bone resorption marker serum beta cross-linked C-terminal telopeptide of type 1 collagen (β-CTX), were measured individually. Normal reference of ALP, Ca, and P [ 19 ] and normal reference of OC and β-CTX [ 20 ] for children involved in the study are listed separately.

The radiographic examinations, including X-rays of the skull, thoracolumbar, and pelvic, were performed in six patients.

Bone mineral density (BMD) was measured by a lunar prodigy dual energy X-ray absorptiometry (DXA) densitometer (Lunar Corp, Madison, WI, USA), including the anteroposterior lumbar spine 1–4 (L1-4), the left proximal femur, and the femoral neck and total hip. These data were analyzed using Prodigy enCORE software (ver. 6.70 standard-array mode; GE Healthcare, Madison, WI, USA). The Z-scores (the number of standard deviations from the mean value for persons in the general population matched for age, sex, and race) were used for children, premenopausal women, and men under age 50.

Genetic analysis and variant prediction

Sanger sequencing was used to detect LRP5 mutations. Genomic DNA was extracted from the 3-mL peripheral blood sample of each participant using phenol extraction and isopropanol precipitation. Sanger sequencing was performed on patients and their family members by BigDye Terminator Cycle Sequencing Ready Reaction Kit v. 3.1 (Applied Biosystems, Foster City, CA, USA) on an ABI 3730XL automated sequencer (Thermo Fisher Scientific, Waltham, MA, USA). The sequencing files were analyzed by PolyPhred software for checking single-nucleotide polymorphisms (SNPs). The results were obtained after manual proofreading. All variants were mapped on transcript NM_002335.2 and protein NP_002326.2.

The ExAC and 1000 Genomes Project databases were used to identify the novel variant. Its amino acid conservation and pathogenicity were analyzed by UniProt databases ( https://www.uniprot.org/ ), PolyPhen-2 ( http://provean.jcvi.org ), and MutationTaster ( https://www.mutationtaster.org/ ).

Structural analysis of LRP5 protein

The protein sequence of LRP5 was obtained from the UniProt database ( https://www.uniprot.org/ ) as a FASTA file. Three-dimensional structure homology modeling and visualization of the native and mutant proteins were performed using AlphaFold software ( https://alphafold.ebi.ac.uk/ ) and Rosetta.

Clinical manifestation

Patient 1 (P1) was a 9-year-old girl born at full-term with healthy non-consanguineous parents. Her psychomotor development was normal. She was congenitally blind. The visual problems were noted at 3 months of age, showing right cataract and left microphthalmia in the ophthalmologic findings (Fig.  2 a). At the age of 9, she had back pain and developed a kyphosis after falling. Radiologic examination showed significant systemic osteoporosis, increased dorsal kyphosis, and multiple vertebral compression fractures (Fig.  3 a). BMD value of L1-4 was 0.363 g/cm 2 , which was significantly lower than the normal range for children of the same age and gender [ 21 ]. Results of biochemical parameters were mainly within the normal range, except for the deficiency of 25(OH)D (Table  1 ). Concurrently, ophthalmic reexamination showed that there was an absence of bilateral optic nerve.

Ocular clinical features of patients with OPPG. a Cataract (right) and microphthalmia(left). b Enucleation of eyeball (right) and cataract (left)

X-rays of the spine and pelvic of OPPG. a Generalized osteoporosis with fish mouth vertebra of patient 1 before treatment. b Improvement of lumbar vertebral body morphology and increased BMD of patient 1 after 3-year alendronate treatment. c Generalized osteoporosis with lumbar scoliosis of patient 2 before treatment and d after 6-month zoledronate treatment

Patient 2 (P2) was the first child born to non-consanguineous parents. She was born blind and was diagnosed with right retinoblastoma and left retinal atrophy. At the age of 13, she underwent enucleation of her left eye due to tumor swelling and retinal perforation (Fig.  2 b). She experienced chronic systemic bony pain and had her first nontraumatic fracture at the manubrium sterni at the age of 9. In the following years, many fractures occurred, including the ribs, humerus, thoracolumbar spine, hip, femur, tibia, and ankle, mainly involving long bones and vertebrae. When she was 16, she could not keep her upper body upright due to multiple vertebral compression fractures. She could stand unsupported but unable to walk independently and must rely on a wheelchair. In addition, she had torn ligaments in her knees and ankles and was also troubled by recurrent aseptic inflammation of her sacroiliac joint.

Besides, she has had frequent premature beats since childhood and developed into paroxysmal atrial fibrillation a few years later, and once had a cardiac arrest. However, no organic lesions were found by cardiac examination.

The results of biochemical parameters including serum calcium, phosphonium, ALP, PTH, and bone turnover markers were summarized in Table  1 . Except vitamin D deficiency, all indicators were within the normal range. Radiologic examination showed thoracolumbar scoliosis, mild compression fractures of the local thoracic spine, and low pelvic BMD (Fig.  3 c). The BMD of L1-4 was 0.630 g/cm 2 , and the Z-score value was − 4. Her parents and brother were healthy and had no vision or skeletal problems.

Identification of LRP5 variants

We verified the mutations in the patients and their family members if they agreed, and the results are presented in Figs. 1 a, b and 6 a. Sanger sequencing confirmed that P1 had a compound heterozygous mutation in exon 7 (c.1455G > T, p.Glu485Asp) and exon 8 (c.1708C > T, p.Arg570Trp) and P2 had a compound heterozygous mutation in exon 6 (c.1145C > T, p.Pro382Leu) and exon 23 (c.4830dupC, p.cys1611leufsx33). Meanwhile, some healthy relatives of the two patients carried a heterozygous mutation from their corresponding family.

Variant prediction and structural analysis

Multiple sequence alignment reveals that Glu485 is highly conserved in different species (Fig.  6 a), and Glu485Asp is predicted as “disease-causing” by PolyPhen-2, MutationTaster, SIFT, and PROVEAN ( Supplementary table ). Furthermore, the three-dimensional structure homology modeling and visualization of the native and the three missense mutant proteins show that the three mutations have no apparent effect on protein structure. As for Pro382Leu, since no hydrogen bonds are formed before and after the mutation, there are no changes at least in the hydrogen bonds formed with neighboring atoms at the mutation site. However, as for Glu485Asp, our AlphaFold result shows there are changes in the length of the hydrogen bonds, while Rosetta result shows the number of hydrogen bonds changed from four in the native type to two in the mutant type. It also forms fewer hydrogen bonds at the site of the Arg570Trp in both modeling results (Fig.  6 b and SI ).

Treatment and follow-up

P1 received oral alendronate treatment at a dose of 70 mg/week from the age of 9 to 12. During the 3-year treatment, bone pain was significantly relieved. The baseline and follow-up serum levels of calcium, phosphorus, bone turnover markers, alkaline phosphatase, and PTH were summarized in Table  2 . All of them were within in the normal level and showed no significant difference. Oral administration of 600 IU of vitamin D3 per day did not improve the state of vitamin D deficiency. The spinal X-ray after treatment showed significant improvement in the shape of the thoracolumbar spine (Fig.  3 b), and there were no new fractures during the treatment. Furthermore, the BMD of L1-4, femur neck, and total hip was significantly increased by 107.2%, 70.0%, and 65.5%, respectively (Table  2 ).

As for P2, she was diagnosed as “osteoporosis” or “osteogenesis imperfecta” in other hospitals and took alendronate 70 mg per week at the age of 13. Six months later, she quit because of recurrence of fractures and no significant improvement in BMD. Last year, at the age of 27, she received 5 mg of zoledronic acid intravenously. Simultaneously, she took vitamin D3 800 IU and calcium 1000 mg per day. The clinical symptoms improved within half a year after injection. She could walk longer without a wheelchair. Although she fell down twice, she did not have a fracture, which was likely to happen in the past. BMD of L1-4, femoral neck, and total hip increased by 5.87%, 6.76%, and 4.15%, and β-CTX and osteocalcin decreased slightly after 6 months of treatment. Serum calcium, phosphorus, and parathyroid hormone levels were almost unchanged. Although the level of 25(OH)D increased, it was still below the normal range (Table  2 ).

No serious adverse drug reactions occurred in both patients during the treatment.

Clinical manifestations

Patient 3 (P3), a 32-year-old male, came to our department because of lumbodorsal pain. A torus palatinus in the center of the oral hard palate was detected by physical examination (Fig.  4 a). X-ray examination revealed that the skull, thoracolumbar vertebrae, and pelvis bones were dense, and the cranial plate was significantly thickened (Fig.  5 a). The Z-scores of BMD of the L1-4, femur neck, and total hip were + 10.5, + 11.1, and + 12.3, respectively ( Table 1 ). The patients have no history of fractures, sensorimotor neuropathy, and visual or hearing impairment. The level of serum calcium, phosphonium, ALP, PTH, 25(OH)D, and bone turnover markers was all within the normal range ( Table 1 ). His family members were all healthy.

Clinical manifestations of patients with LRP5-HBM. a , b , c The torus palatinus in the center of the hard palate of 3 patients. d A slight depression in the right chest of patient 4

X-rays of the skull, spine, humerus, and femur of two LRP5-HBM patients ( a : patient 3; b : patient 4). Osteosclerosis of the skull with an enlarged sella turcica. Generalized osteosclerosis. Cortical thickening of the humerus and femur with a normal external shape

Patient 4 (P4) was a 6-year-old boy born at full-term who was found to have thoracic deformity at the age of 3. He was diagnosed as “Rickets” in the local hospital, but the symptoms did not improve after calcium and vitamin D supplementation. At the age of 6, the abnormal increased bone mineral density of ribs, sternum, thoracic vertebrae, and bilateral humeral metaphysis was identified by occasionally chest X-ray examination due to cough. In order to confirm the diagnosis, the child underwent further radiological examination. The examination found that the patient’s whole-body BMD increased and the skull plate thickened (Fig.  5 b). The patient had normal tooth development and maxillary morphology. No jaw enlargement or palatal ring was found. The patient had a slight depression on the right side of the chest (Fig.  4 d) and had no history of fracture.

Moreover, the value of BMD of L1-4, femoral neck, and total hip was 1.149 g/cm 2 , 1.327 g/cm 2 , and 1.321 g/cm 2 , respectively (Table  1 ). The biochemical indices including serum calcium and phosphonium, ALP, PTH, 25(OH)D, β-CTX, and OC were within the normal range (Table  1 ).

His parents were healthy and non-consanguineous.

Patients 5 and 6

Patients 5 (P5) and 6 (P6) were a mother-daughter pair, as reported in our previous study [ 18 ]. In brief, both of them had chronic lumbodorsal pain, an elongated mandible and torus palatinus (Fig.  4 b and c), high bone mass, but no history of fractures. X-ray radiographs showed thickening of the cranial plates, an elongated mandible, cortical thickening of the long bones, and degenerative changes. The biochemical indices showed that they both had vitamin D deficiency. The serum ALP level of patient 6 was slightly higher than normal range, while β-CTX was much higher than the normal range (Table  1 ).

The LRP5 gene detection results of patients and their family members were shown in Figs. 1 c, d, and e and 6 a. By Sanger sequencing, the heterozygous c.724G > A (p.Ala242Thr) mutation was detected in P3, P5, and P6. And the heterozygous c.640G > A (p.Ala214Thr) mutation was detected in P4. We did not identify any pathogenic variants in family members other than the patients.

Sanger sequencing and the three-dimensional modeling. a Multiple sequence alignments revealed that the glu485 residue in the LRP5 protein was highly conserved among species; Sanger sequencing of the LRP5 mutations: p.Glu485Asp (E485D, c.1455G > T) and p.Arg570Trp (R570W, c.1708C > T) in patient 1; p.Pro382Leu (P382L, c.1145C > T) and p.Cys1611LeufsX33 (c.4830dupC) in patient 2; p.Ala242Thr (A242T, c.724G > A) in patients 3, 5, and 6; p.Ala214Thr (A214T, c.640G > A) in patient 4. b Comparison of the three-dimensional modeling of wild and missense mutations’ local structures by AlphaFold; distribution of the six mutation sites on the LRP5 protein

Structural analysis

As predicted by AlphaFold and Rosetta, the conversion of alanine to threonine in two mutation sites has no apparent effect on protein structure. But in the modeling results of both software, the number of hydrogen bonds increases after the mutations (Fig.  6 b and SI ).

P5 underwent 12 years of follow-up. During the follow-up period, pain in the thoracolumbar spine, cervical spine, and shoulders was the main issue, but there were no fractures, no dental problems, and no significant changes in height. In addition, no neurological symptoms such as trigeminal neuralgia, neurogenic hearing loss, visual field deficits, or chronic headaches occurred during the follow-up period. She only takes painkillers when necessary to relieve her lower back pain. In the past year, she has experienced menstrual cycle disorders. After 12 years of diagnosis, the patient underwent a reexamination of BMD, bone turnover markers, and biochemical parameters. The detailed results were summarized in Table  3 . Compared with the results 12 years ago, the absolute value of BMD of L1-4, femoral neck, and total hip was decreased by 9.62%, 12.81%, and 11.03%, respectively, but it was still higher than the reference value of the same age and gender. The serum levels of PTH, Ca, and P were normal, but 25(OH)D is still below the normal range. Bone turnover markers, including β-CTX and OC, were higher than the normal range.

In the current study, we reported five mutations and a variant, four from OPPG patients (Glu485Asp, Arg570Trp, Pro382Leu and Cys1611LeufsX33) and two from LRP5-HBM patients (Ala242Thr and Ala214Thr). Glu485Asp, Arg570Trp, and Pro382Leu all lie in the exons collectively coding for the second β-propeller domain, consistent with that most OPPG mutations reported have been described in the second and third b-propeller domains [ 22 ]. However, Cys1611LeufsX33 lies in the intracellular domain, which is supposed to be phosphorylated and therefore inhibit GSK3b when Wnts bind to its coreceptors Frizzled and LRP6/5 [ 23 ]. In addition, the novel variant Glu485Asp is considered to be pathogenic after conservation and pathogenicity prediction, which broadens the variation spectrum of pathogenic genes. Ala242Thr and Ala214Thr are the hot spot mutations in patients with LRP5-HBM [ 3 , 14 , 18 ], both located in the amino terminal part of the gene, before the first EGF-like domain, like the previously reported mutations that cause the high-bone-mass phenotype. Besides, Ala242Thr has been predicted to incline to disrupt the core packing of the LRP5 protein structure and affect the first β-propeller domain, thereby destabilizing the binding site of SOST and LRP5 [ 24 ]. We performed the three-dimensional structure homology modeling and visualization of the native and five missense mutant proteins using the online AlphaFold and Rosetta software. Glu485Asp, Arg570Trp, Ala214Thr, and Ala242Thr all had variations in the number or length of hydrogen bonds. Interestingly, we found that the number of hydrogen bonds at the mutation site decreased in the loss-of-function mutation (Glu485Asp and Arg570Trp), while they increased in the gain-of-function mutation (Ala214Thr and Ala242Thr), which may be associated with the loss and gain of LRP5 function. Modeling of Pro382Leu by two software showed no significant changes in structure and hydrogen bonding before and after mutation, but case reports of both homozygous and compound heterozygous mutations of Pro382Leu have been reported [ 25 , 26 ]. Its effect on the local structure of LRP5 protein and the intensity of Wnt signaling pathway remained unclear. Cys1611LeufsX33 was a frameshift mutation where termination codon was shifted back. And the mutation was located at the site where LRP5 intracellular structure binds to Wnts and Frizzled, which might have a great influence on the transmission of the intracellular part of Wnt signal.

OPPG children may sometimes be misdiagnosed as osteogenesis imperfecta, but they have no identifiable defects in collagen synthesis and metabolism, with their calcium homeostasis, endochondral growth, and bone turnover index all normal [ 27 , 28 ]. It is worth mentioning that P2 has developed nonorganic paroxysmal atrial fibrillation of unknown cause in recent years, which is not found in other OPPG patients reported. Besides, neurological diseases such as seizures, autism spectrum disorder, and intellectual deficit in individual OPPG cases are reported abroad [ 29 , 30 , 31 ], but there are not such problems in OPPG patients reported in our country [ 32 ], including the two patients in present study. It is still unclear whether the clinical variability of neurological phenotypes can be attributed to mutational effects or a specific protein domain [ 10 , 33 ].

At present, there are few treatment options for OPPG children. Bisphosphonates are the most commonly used and rational drug for them, and its effect on improving the bone condition has been confirmed [ 9 , 30 ]. In the present study, the beneficial effects have been observed in the 3-year alendronate sodium for P1 and half-year intravenous zoledronic acid for P2. During and after bisphosphonate treatment, for both the biochemical indexes and hormone values were basically within the normal range, the symptoms were improved, and the risk of fracture was reduced. However, P2 experienced a period of failed oral alendronate treatment before the zoledronic acid, manifested by the appearance of new fractures and unrelieved bone pain. Actually, in this case, the drug adjustment should be determined according to a combination of factors, including fracture history, bone pain, growth, and bone mineral density.

In the present study, high bone mass, torus palatinus, and an elongated mandible were the most common clinical symptoms for our LRP5-HBM patients. The serum ALP of all patients was within the normal range, and no symptoms of nervous system were involved. Interestingly, the 6-year-old patient (P4) did not have torus palatinus but had thoracic deformity, which had never been reported in cases of LRP5-HBM, and it was uncertain whether it was caused by LRP5 gene mutation.

In the current study, we found that P5 has entered a period of rapid bone turnover; β-CTX and OC were out of normal range. The BMD of L1-4 decreased by 9.6% within 12 years, with an average annual decrease of 0.8%. Considering that our patient has been in the late perimenopause stage (no menstrual bleeding in the last 3 months but some menstrual bleeding during the last 11 months), the menstrual disorder in the past year may partly be the reason for the decrease of bone mass and the acceleration of bone turnover. Since there were no long-term longitudinal studies on changes in bone mineral density during the perimenopausal transition in mainland Chinese women, we used data collected from women in Chinese Hong Kong [ 34 ] as a reference, from which we estimated that the lumbar spine bone loss rate of healthy women population from age 40 to 52 is about 7.94%. Anyhow, it seemed that our patient did not seem to lose bone at a slower rate than healthy controls, and the gain-of-function mutation Ala242Thr could not protect her from age-related and estrogen-related bone loss. Similarly, another study found that individuals with LRP5 T253I -HBM were not protected from age-related bone loss, at least at the hip and femoral neck [ 35 ]. Whether LRP5 gain-of-function mutations can actually help carriers resist bone loss due to bone wasting factors, and whether this effect is related to the mutation site needs more follow-up data to be confirmed.

In the current study, two cases of OPPG caused by LRP5 loss-of-function mutations and four cases of LRP5-HBM caused by LRP5 gain-of-function mutations were reported. For OPPG, a novel heterozygous missense mutation was reported to expand the genotypic spectrum of OPPG. The bisphosphonates treatment can increase the BMD and decrease the risk of fracture for patients with OPPG. On the other hand, LRP5-HBM is a relatively benign disease. LRP5 gene mutation, however, may not slow down the rate of bone loss, including postmenopausal bone loss. This phenomenon deserves further observation and study.

Data availability

The data that support the findings of this study are available on request from the corresponding authors. The data are not publicly available due to privacy or ethical restrictions.

Hussain MM, Strickland DK, Bakillah A (1999) The mammalian low-density lipoprotein receptor family. Annu Rev Nutr 19:141–172

Article   CAS   PubMed   Google Scholar  

Baron R, Rawadi G, Roman-Roman S (2006) Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol 76:103–127

Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Bénichou O, Scopelliti D et al (2003) Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet 72(3):763–771

Article   PubMed   PubMed Central   Google Scholar  

Baron R, Kneissel M (2013) WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 19(2):179–192. https://doi.org/10.1038/nm.3074

Balemans W, Piters E, Cleiren E, Ai M, Van Wesenbeeck L, Warman ML et al (2008) The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int 82(6):445–453. https://doi.org/10.1007/s00223-008-9130-9

Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM et al (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107(4):513–523

Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA et al (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346(20):1513–1521

Patel MS, Karsenty G (2002) Regulation of bone formation and vision by LRP5. N Engl J Med 346(20):1572–1574

Zacharin M, Cundy T (2000) Osteoporosis pseudoglioma syndrome: treatment of spinal osteoporosis with intravenous bisphosphonates. J Pediatr 137(3):410–415

Ai M, Heeger S, Bartels CF, Schelling DK (2005) Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet 77(5):741–753

Article   CAS   PubMed   PubMed Central   Google Scholar  

Levasseur R, Lacombe D, de Vernejoul MC (2005) LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint Bone Spine 72(3):207–214

Article   PubMed   Google Scholar  

Lee DH, Wenkert D, Whyte MP, Trese MT, Cruz OA (2003) Congenital blindness and osteoporosis-pseudoglioma syndrome. J AAPOS 7(1):75–77

Gorlin RJ, Glass L (1977) Autosomal dominant osteosclerosis. Radiology 125(2):547–548

De Mattia G, Maffi M, Mosca M, Mazzantini M (2023) LRP5 high bone mass (Worth-type autosomal dominant endosteal hyperostosis): case report and historical review of the literature. Arch Osteoporos 18(1):112. https://doi.org/10.1007/s11657-023-01319-6

Lapresle J, Maroteaux P, Kuffer R, Said G, Meyer O (1976) Dominant generalized cortical hyperostosis with multiple involvement of the cranial nerves. Nouv Presse Med 5(40):2703–2706

CAS   PubMed   Google Scholar  

Adès LC, Morris LL, Burns R, Haan EA (1994) Neurological involvement in Worth type endosteal hyperostosis: report of a family. Am J Med Genet 51(1):46–50

Perez-Vicente JA, Rodríguez de Castro E, Lafuente J, Mateo MM, Giménez-Roldán S (1987) Autosomal dominant endosteal hyperostosis. Report of a Spanish family with neurological involvement. Clin Genet 31(3):161–9

Wang C, Zhang B-H, Zhang H, He J-W, Hu Y-Q, Li M et al (2013) The A242T mutation in the low-density lipoprotein receptor-related protein 5 gene in one Chinese family with osteosclerosis. Intern Med 52(2):187–192

Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A et al (2007) Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab 92(2):443–449

Huang Y, Eapen E, Steele S, Grey V (2011) Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem 44(10–11):771–778. https://doi.org/10.1016/j.clinbiochem.2011.04.008

Zhu H, Fang J, Luo X, Yu W, Zhao Y, Li X et al (2010) A survey of bone mineral density of healthy Han adults in China. Osteoporos Int 21(5):765–772. https://doi.org/10.1007/s00198-009-1010-2

Rickels MR, Zhang X, Mumm S, Whyte MP (2005) Oropharyngeal skeletal disease accompanying high bone mass and novel LRP5 mutation. J Bone Miner Res 20(5):878–885

Piao S, Lee S-H, Kim H, Yum S, Stamos JL, Xu Y et al (2008) Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling. PLoS ONE 3(12):e4046. https://doi.org/10.1371/journal.pone.0004046

Gregson CL, Wheeler L, Hardcastle SA, Appleton LH, Addison KA, Brugmans M et al (2016) Mutations in known monogenic high bone mass loci only explain a small proportion of high bone mass cases. J Bone Miner Res 31(3):640–649. https://doi.org/10.1002/jbmr.2706

Astiazarán MC, Cervantes-Sodi M, Rebolledo-Enríquez E, Chacón-Camacho O, Villegas V, Zenteno JC (2017) Novel homozygous LRP5 mutations in Mexican patients with osteoporosis-pseudoglioma syndrome. Genet Test Mol Biomarkers 21(12):742–746. https://doi.org/10.1089/gtmb.2017.0118

Narumi S, Numakura C, Shiihara T, Seiwa C, Nozaki Y, Yamagata T et al (2010) Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray. Am J Med Genet A 152A(1):133–40. https://doi.org/10.1002/ajmg.a.33177

Levasseur R (2008) Treatment and management of osteoporosis-pseudoglioma syndrome. Expert Rev Endocrinol Metab 3(3):337–348. https://doi.org/10.1586/17446651.3.3.337

Teebi AS, Al-Awadi SA, Marafie MJ, Bushnaq RA, Satyanath S (1988) Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association. J Med Genet 25(1):32–36

Laine CM, Chung BD, Susic M, Prescott T, Semler O, Fiskerstrand T et al (2011) Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). Eur J Hum Genet 19(8):875–881. https://doi.org/10.1038/ejhg.2011.42

Karakilic-Ozturan E, Altunoglu U, Ozturk AP, Kardelen Al AD, Yavas Abali Z, Avci S et al (2022) Evaluation of growth, puberty, osteoporosis, and the response to long-term bisphosphonate therapy in four patients with osteoporosis-pseudoglioma syndrome. Am J Med Genet A 188(7):2061–2070. https://doi.org/10.1002/ajmg.a.62742

Welinder LG, Robitaille JM, Rupps R, Boerkoel CF, Lyons CJ (2015) Congenital bilateral retinal detachment in two siblings with osteoporosis-pseudoglioma syndrome. Ophthalmic Genet 36(3):276–280. https://doi.org/10.3109/13816810.2015.1016240

Bai Z, Jiao Z, Kong X (2022) Analysis of LRP5 gene variants in a Chinese pedigree affected with osteoporosis-pseudoglioma syndrome. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 39(2):185–188. https://doi.org/10.3760/cma.j.cn511374-20201125-00828

Papadopoulos I, Bountouvi E, Attilakos A, Gole E, Dinopoulos A, Peppa M et al (2019) Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece. Eur J Pediatr 178(3):323–329. https://doi.org/10.1007/s00431-018-3299-3

Tang GW, Yip PS, Li BY (2001) The profile of bone mineral density in chinese women: its changes and significance in a longitudinal study. Osteoporos Int 12(8):647–653

Lauterlein J-JL, Gossiel F, Weigl M, Eastell R, Hackl M, Hermann P et al (2021) Development of the bone phenotype and microRNA profile in adults with low-density lipoprotein receptor-related protein 5-high bone mass (LRP5-HBM) disease. JBMR Plus 5(9):e10534. https://doi.org/10.1002/jbm4.10534

Download references

This work was supported by the National Key R&D Program of China (2018YFA0800801) and the National Natural Science Foundation of China (81770872 and 82170895).

Author information

Authors and affiliations.

Department of Osteoporosis and Bone Disease, Shanghai Clinical Research Center of Bone Disease, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai, 200233, China

Na Ren, Shanshan Lv, Xiang Li, Chong Shao, Ziyuan Wang, Yazhao Mei, Wendi Yang, Wenzhen Fu, Yunqiu Hu, Ling Sha, Weiwei Hu, Zhenlin Zhang & Chun Wang

You can also search for this author in PubMed   Google Scholar

Corresponding authors

Correspondence to Zhenlin Zhang or Chun Wang .

Ethics declarations

Consent to participate.

Written informed consent was obtained from the patient to publish this case report and any accompanying images.

Conflicts of interest

Additional information, publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (TIF 16432 KB)

Supplementary file2 (docx 13 kb), rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ .

Reprints and permissions

About this article

Ren, N., Lv, S., Li, X. et al. Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass. Osteoporos Int (2024). https://doi.org/10.1007/s00198-024-07080-x

Download citation

Received : 31 January 2024

Accepted : 30 March 2024

Published : 16 April 2024

DOI : https://doi.org/10.1007/s00198-024-07080-x

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• High bone mass
• Osteoporosis
• Find a journal
• Publish with us
• Track your research

• Osteoporosis & Bone Health

Risks of Hip Surgery with Osteoporosis

I have osteoporosis in my left hip (neck region) with a T score of -2.7. I know that I'm looking at a hip replacement at some point & wondered if anyone has had a hip replacement with osteoporosis. I'm beginning the process of checking out orthopedic surgeons for a consultation. I need to understand the risks involved. I'm 68 & exercise regularly. I'm noticing my hip is not as nimble as it used to be & in recent months is painful after sitting for any length of time (such as watching TV in the evening). It feels great standing & when I'm moving. Has anyone had hip replacement surgery with osteoporosis? What can you share about your experience?

• Copy link to clipboard
• Report discussion

Interested in more discussions like this? Go to the Osteoporosis & Bone Health Support Group.

sugarmonkey, are you on an anabolic drug for osteoporosis. You might want to be on one for several months before surgery. Forteo and Tymlos are good choices. You'd possibly save yourself from surgery.

• Report comment

sugarmonkeys, I have osteoporosis and have been on Evenity for 11 months. In June 2023, I had a right hip replacement. Before the surgery, I asked the surgeon about my mushy hip bone and the surgery. I had watched a video of a hip replacement surgery - not for the faint hearted. He said that he would use some additional hardware if necessary. As it turned out, that wasn’t necessary. The hip replacement was a big success and has restored my mobility. I still have osteoporosis, but will not be fracturing that titanium hip.

I wonder if -2.7 presents a problem. That is not severe, but it is osteoporosis. What does your doctor say?

I have pain lying down or sitting, and it is from a bone spur, not a joint issue. The bone spur is extra bony growth that presses on a nerve when I sit or lie down. Have you had imagining done? You seem to know it is the femur neck at issue...

How disabled are you? I am still avoiding surgery for spine and hip but there is an argument to get ahead of it. You could do a bone builder like Forteo, Tymlos or Evenity. The first two also help with healing, so I have no idea what the sequence should be. Hope the ortho and endo can communicate!

I saw an orthopedist who does not do surgery, for an opinion. He does lidocaine shots but they didn't help. They help most people though.

@sugarmonkeys - it’s unclear if you are just thinking a hip replacement is in your future , or if that’s something a physician has said to you. If you have n’t seen anyone , I agree with windyshores , you should make an appt cause you may be stressing about something that’s not even in the cards. I went to see a very good sports medicine physician that works within an orthopedic practice. I wanted to see someone that has tools in his tool chest other than surgery. But keep in mind there are lots of reasons for hip inflexibility and pain. You might even want to first start with a good orthopedic PT , then sports med physician , then orthopedic surgeon if needed as your situation begins to be figured out. Keep in mind there are many reasons and underlying issues that can cause those types of complaints at the hip. It’s a complex joint area. Good luck!!

Jump to this post

@ans makes a great suggestion. I have gotten more diagnostic info and pain relief from a really good PT, who does massage (manual therapy)and ultrasound.

Orthopedists who don't do surgery are good resources with no investment in what you decide!! Not that surgeons are unethical, just that they lean toward that kind of action.

Thank you all for your comments. I am not disabled, just achy when I stand up from sitting. I've been studying to be an Aquatics Fitness instructor which entails a lot of reading (over 300-page book, 100 pages of typewritten notes & lots of studying). So, I've been sitting way too much. I'm now in the memorization mode so standing while studying which helps.

My Sports Medicine Orthopedist whom I saw a few weeks ago gave these options: 1. Modify activities (avoid high impact). 2. Intra articular steroid injections (1 injection per week for 3 weeks). 3. Surgical intervention. He did not say I needed surgery. I'm just wanting to understand what the risks are when that time comes. Physical therapy is a good idea. It may be the arthritis that is bothering me the most. I have it in both hips, as well as other parts of my body. I also remember having an inflamed bursa in my hip back in 2005.

I've had osteopenia since my 40s & was diagnosed with osteoporosis since 2014. Sometimes my Dexa scans show that it's getting better & sometimes it shows it's getting worse. One technician told me that you could have 2 Dexa scans in a row & may get different readings. My Arthritis doctor told me to always get my Dexa scans at the same place because different machines could give different readings. Good to know. I'm due for one a Dexa scan this Fall.

I was on Fosamax for several years & my Arthritis doctor took me off of it because she said that you can only take it for so long because it stays in your system for 10 years. Then, it does the opposite of what it's supposed to do. Therefore in 2015, my Arthritis doctor suggested Reclast infusions. I have had Reclast infusions 3 times over a period of 6 years. The last infusion was last year. My side effect from Reclast is that it's thins my hair which is annoying. Steroids does the same thing. My Arthritis doctor has suggested Evenity but I'm stalling due to the cost & concerns about her suggesting Prolia after the 12 months of Evenity infusions. Currently, I'm not taking anything besides Calcium & Vitamin D.

I'm trying to educate myself on future actions & I notice this forum is very helpful. Thank you again for your assistance. It is greatly appreciated.

@sugarmonkeys I am a little confused by your post. You have had osteoporosis since 2014, took Fosamax for several years, and did Reclast in 2015. That is only one year after your diagnosis. So did you take Foasamax before you had osteoporosis?

If a doctor said you should stop Fosamax and switch to Reclast, that is very confusing also because they are similar medications- bisphosphonates- except that Reclast is stronger. So you have been on bisphosphonates for 10 years now, which I have read is kind of the limit. Bisphosphonates are anti-resorptive and affect turnover.

Evenity is also anti-resorptive for the last 6 months. There is a study out using Evenity for only 6 months and then "locking in" gains with Reclast or Fosamax (or Prolia). Wonder if your doctor would allow that.

Tymlos and Forteo build quality bone and might be an option- ask you doctor. Previous bisphosphonates can affect their effectiveness (and that of Evenity too, but about 1/3 I read) but one of these drugs (Tymlos) was very helpful to me. Again, you have to "lock in" with Reclast or Fosamax.

Prolia is often suggested as a follow-up but is difficult to get off without rebound, and also has to be followed by Reclast or Fosamax. I figure once I hit 85 I would do Prolia because presumably I would never have to get off!

Doing bisphosphonates for so long leaves you in a tough place but there are some really good medications that you could try and then hopefully only do a dose or two of Reclast at the end of those meds, according to what my doctor is saying to me.

People do get put on Fosamax for osteopenia. It happened to a friend of mine and she ended up with fractures due to being on it too many years,

@normahorn two friends of mine were recently told to take Fosamax with osteopenia in one case, and borderline in the other. I didn't think doctors were doing that anymore but they certainly were before the other meds we now have, were available. I guess they still are. Maybe it is a good thing for borderline cases-?

I don't know what I would do with scores like -2.7 or -2.9. @sugarmonkeys I forgot you were at -2.7.

It is becoming clear that sequencing and duration are issues for all of us. All these meds have limited time we can take them so unless we are very old, not sure what we are going to be doing for treatment in the long run.

@sugarmonkeys I hope you get good answers!

@windyshores sorry for the confusion. I was not clear. I took Fosamax when I was first diagnosed with osteopenia in the early 2000s to around 2013. I will ask my doctor about Tymlos & Forteo. I am not familiar with either of those drugs. Thank you.

Connect with thousands of patients and caregivers for support and answers.

• Hosted and moderated by Mayo Clinic.
• Safe and secure.

Already have an account? Sign In