Brief rationale: Osteoporosis management in Italy shows regional inconsistencies. Expert surveys and meetings revealed limited access to anabolic treatments and fragmented care pathways. Significance of the paper: Findings support the need for updated national guidelines to promote equitable care and reduce the burden of osteoporotic fractures. Osteoporosis is a progressive bone disease characterized by reduced bone density and increased fracture risk, significantly affecting quality of life and imposing a substantial burden on healthcare systems. In Italy, managing osteoporosis is a national priority due to the rising incidence of fractures among the aging population. This study evaluates clinical practices in osteoporosis management across Northern, Central, and Southern Italy, focusing on diagnostics, therapies, and access to specialized care. A detailed survey was distributed across multiple centers to evaluate diagnostic, therapeutic, and follow-up practices, along with specialists' perspectives on national guidelines and the challenges in accessing advanced treatments. Following the survey, three regional expert meetings were held to analyze the findings and gain further insight. Findings show widespread use of bone mineral density (BMD) testing and laboratory assessments, with regional differences in the use of fracture risk tools (FRAX, DeFRA) and markers such as CTX. Bisphosphonates, denosumab, and anabolic agents are commonly used; however, significant disparities persist in access to anabolic treatments. The patient journey remains uneven across regions, with challenges in accessing bone specialists, timely diagnosis, and appropriate treatment. In areas lacking structured care pathways, these gaps lead to delayed or suboptimal management. These findings highlight the need for updated, flexible guidelines to support a tailored and equitable approach to osteoporosis care in Italy. Improving access to specialized care and standardizing treatment pathways may enhance outcomes and reduce healthcare costs associated with osteoporosis-related fractures.
PURPOSE OF REVIEW: This review aims to summarise the current application and development trends of artificial intelligence in opportunistic screening for osteoporosis, with a focus on its potential to improve early detection and management of the disease. RECENT FINDINGS: Recent advancements in AI, including radiomics, deep learning, and transfer learning, have significantly enhanced the efficacy of opportunistic screening for osteoporosis. Imaging modalities such as chest X-rays, lumbar X-rays, chest CT, hip joint CT, PET-CT, and lumbar magnetic resonance imaging have been successfully integrated into AI-driven screening protocols. These technologies have demonstrated acceptable efficacy in detecting osteoporosis, with the potential to increase the probability of identifying at-risk individuals. The evolution of image processing and segmentation techniques further supports the prospect of achieving fully automated AI-based opportunistic screening in the near future. The integration of AI into opportunistic screening for osteoporosis shows promise in improving early detection rates, particularly in aging populations. Achieving automatic segmentation of Region of Interest areas based on common medical imaging is a critical step in enabling opportunistic osteoporosis screening using artificial intelligence.
Rat models are widely used in preclinical osteoporosis research to study disease mechanisms and evaluate therapies. Current Micro-CT studies mostly rely on cross-sectional comparisons at a single time point, and there is a lack of standardized reference data across multiple time points. To address this gap, the present study provides standardized reference data from multiple time points using a deep learning-based Micro-CT grayscale analysis, enabling early detection and precise staging of osteoporosis. A standardized osteoporosis model was established in ovariectomized Sprague-Dawley rats (n = 32) with a sham-operated group (n = 32). Femurs were harvested at 4, 8, 16, and 24 weeks post-surgery. The proximal 0-250 slice region adjacent to the growth plate was defined as the region of interest (ROI), and six representative slices per femur were analyzed. Voxels within each ROI were classified into four grayscale regions: 0-50 (non-bone), 51-100 (bone-nonbone transition), 101-150 (defined bone), and 151-255 (highly mineralized bone). The percentage areas of the four regions across the six slices (4 × 6 input) were used to train a custom deep learning model. Diagnostic performance for early osteoporosis detection and staging was compared with conventional trabecular parameters. Both the grayscale-based algorithm and conventional Micro-CT parameters distinguished Sham and OVX rats at 4 weeks, enabling early detection, whereas DXA only detected differences at 16 weeks. In osteoporosis staging within the OVX group, the grayscale-based model achieved higher accuracy (88.4 % ± 6.4 %) than conventional parameters (55.9 % ± 8.4 %, p < 0.05). For single-time-point osteoporosis diagnosis, the grayscale-based algorithm (98.3 % ± 3.4 %) also outperformed conventional parameters (85.3 % ± 3.4 %, p < 0.05). The grayscale-based deep learning method allows sensitive early detection and more accurate staging of osteoporosis, providing a robust quantitative tool for assessment of osteoporotic progression in OVX rats.
BACKGROUND: Postmenopausal osteoporosis usually happens 5 ~ 10 years after menopause. Low awareness, low detection rates and high morbidity have prevented the possibility of early or preventive interventions, thus increasing the social and economic burden on families and societies. A reliable prediction model for postmenopausal osteoporosis has the potential to guide the prevention, but regarding the early prediction of postmenopausal osteoporosis without fracture, this field has not been sufficiently studied. Although many scholars have developed several prediction models to estimate the risk of postmenopausal osteoporosis without fractures, the evidence about the model quality and clinical applicability is scarce. METHOD: Nine databases (Medline, Embase, Web of science, CINAHL, The Cochrane Library, CNKI, SinoMed, Wanfang, VIP data) were systematically searched from 1 January 2014 to 1 May 2024. Two researchers independently extracted data using the CHARMS checklist and assessed bias using the PROBAST tool. The primary outcomes of interest were related to the model’s discriminative ability (assessed by pooled AUC values) and calibration performance (evaluated using calibration curves or the calibration intercept and slope). We performed meta-regression and sensitivity analyses to explore the influence of important factors, such as data sources, machine learning methods, and types of predictor variables, on the aforementioned. results. Additionally, subgroup analyses were conducted based on data sources, machine learning. methods, and types of predictor variables. The study was registered in the PROSPERO database (registration number CRD42024542498). RESULTS: A total of 8,549 records were initially identified, and 7 studies (comprising 19 models) were ultimately included. All models were developed based on Asian population data. The risk of bias assessment showed: 1 study had a low risk, 1 study had an unclear risk, and 5 studies had a high risk. The sample sizes ranged from 319 to 4,417 participants. The reported AUC of the models ranged from 0.639 to 0.921; however, the vast majority of studies lacked reports on calibration performance. The pooled C-statistic (AUC) was 0.78 (95%CI: 0.73–0.83). Sensitivity analysis yielded robust results (AUC=0.77). Subgroup analysis indicated that models combining demographic and laboratory data demonstrated the best performance (AUC=0.92). Significant publication bias and substantial heterogeneity (I² = 98%) were observed among the studies. CONCLUSION: Current machine learning-based prediction models for postmenopausal osteoporosis without fractures, as presented in the included studies, demonstrate good discriminative ability but are generally characterized by a high risk of bias, a notable lack of calibration performance evaluation, and insufficient validation of clinical utility. Furthermore, existing models are developed entirely on Asian population data, which limits their generalizability to other populations. Future research should focus on strictly adhering to prediction model research guidelines (such as PROBAST), enhancing the reporting of model calibration and clinical utility, and assessing model generalizability through external validation in multi-center studies encompassing diverse ethnicities and regions.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by painful nodules and abscesses in intertriginous areas, predominantly affecting women. Persistent systemic inflammation and hormonal changes may contribute to reduced bone health and an increased risk of osteoporosis in this population. To highlight osteoporosis as an underrecognized comorbidity in women with HS and discuss contributing inflammatory, hormonal, and lifestyle-related risk factors that may predispose patients to bone compromise. A narrative review of the literature was conducted examining the relationship between HS, chronic inflammation, menopause-related estrogen decline, and osteoporosis risk. Additional contributory factors commonly associated with HS, including tobacco use, vitamin D deficiency, obesity, physical inactivity, and repeated corticosteroid exposure, were evaluated. Systemic inflammation, hormonal decline, corticosteroid exposure, vitamin D deficiency, and reduced activity may contribute to increased osteoporosis risk in women with HS. Current evidence evaluating osteoporosis risk specifically in patients with HS remains limited, and additional prospective studies are needed to better characterize prevalence, mechanisms, and screening recommendations. Bone health should be considered in women with HS, particularly those with severe or longstanding disease.
In this meta-analysis of international cohorts, current smoking is confirmed as a significant BMD-independent predictor of future fracture with a stronger relationship in men than in women. A causative and reversible effect of smoking on fracture risk is suggested by past smoking having a significantly lower risk than current smoking. In this meta-analysis of international cohorts, the aim was to examine the relationship of current and past smoking with fracture risk to provide an update for future iterations of the FRAX tool. The risk of fracture associated with current and past smoking was estimated using an extended Poisson model applied separately to each of 58 prospective international cohort studies. Covariates included current time since start of follow up, current age, and in an additional model, BMD at the femoral neck. The results of the different studies were merged by using inverse-variance weighted β-coefficients. This analysis included a total of 1,691,024 participants (61.2% women, overall mean age 58.8 years). Current smoking, documented in 12.1% of all participants (15.2% and 10.1% respectively in men and women), was associated with a significantly increased risk of any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and particularly hip fracture in both sexes. The hazard ratio (HR) for fracture was greater in men than in women for all fracture categories [e.g. hip fracture HR (95% confidence interval): 1.78 (1.58-2.00) vs. 1.64 (1.50-1.78)]. Low BMD explained about 19-54% of the increase in risk. When compared with never smoking, past smoking was associated with a significantly lower risk than current smoking [e.g. hip fractures for men, HR in past smokers: 1.08 (1.05-1.12) vs. 1.73, 95%CI (1.46-2.05) in current smokers]. Our results confirm the association between current smoking and increased fracture risk that is partly independent of BMD; these data will be used to inform future iterations of FRAX.
Osteoporosis affects more than 53 million Americans and contributes to nearly 2 million fragility fractures each year, yet most patients who sustain fractures never receive guideline-recommended pharmacotherapy. Traditional step-therapy typically begins with bisphosphonates and reserves anabolic agents for later-line use, whereas sequential therapy prioritizes anabolic treatment followed by antiresorptive consolidation. This review synthesizes the evidence comparing these treatment paradigms and examines their relevance to orthopedic populations, in whom bone quality directly influences fracture healing, fixation, fusion, and implant-related outcomes. Among 37 studies meeting PRISMA-ScR inclusion criteria, anabolic-first sequential therapy generally produced greater gains in bone mineral density and greater fracture risk reduction than step-therapy or antiresorptive monotherapy. In one representative trial, romosozumab followed by denosumab achieved a 16.8% increase in lumbar spine bone mineral density versus 7.5% with monotherapy, and 92% versus 47% of patients reached treatment targets. In ARCH, anabolic-first therapy was associated with 48% lower vertebral fracture risk and 38% lower hip fracture risk. In orthopedic settings, emerging evidence suggests that sequential protocols may improve postoperative bone mineral density after hip fracture, support spinal fusion, and mitigate periprosthetic bone loss after arthroplasty. Prior antiresorptive exposure appeared to attenuate subsequent anabolic response, particularly at the hip, supporting the rationale for earlier anabolic use. Economic analyses also suggest that, despite higher upfront drug costs, sequential therapy may be cost-effective in patients at high fracture risk. Current evidence supports anabolic-first sequential therapy as a more effective strategy than step-therapy for improving bone mineral density and reducing fracture risk in appropriately selected high-risk patients. For orthopedic populations, the available data suggest meaningful potential benefits in hip fracture care, spinal reconstruction, and arthroplasty, although subspecialty-specific evidence remains more limited than the broader osteoporosis literature. These findings support reconsideration of formulary and treatment policies that delay anabolic therapy in patients most likely to benefit.
This study aimed to investigate the potential of Cone Beam Computed Tomography (CBCT) parameters to identify primary osteoporosis in jawbones. Early diagnosis of osteoporosis is crucial but challenging. Dual X-ray Absorptiometry (DXA) is the gold standard to measure bone density, nevertheless it has limitations including cost, radiation dose, and 2D imaging. CBCT is a volumetric imaging technique commonly used in dentistry that showed promise as an alternative tool due to its high spatial resolution and excellent analysis of bone structures. Mandibular and maxillary CBCT indices showed a strong correlation with Bone Mineral Density (BMD) assessed by DXA. Regional indices (Anterior, Molar, and Posterior), quantitative indices (Computed Tomography Mandibular Index, Computed Tomography Index Superior and Inferior), Radiographic Density, Fractal Dimension, and the qualitative index named Computed Tomography Cortical Index seemed appropriate for the detection of primary osteoporosis. Morphometric parameters for trabecular bone did not show differences between osteoporotic and non-osteoporotic patients. Future studies should assess diagnostic accuracy of such CBCT indices and formulate standardized measurement protocols.
We evaluate the converging evidence positioning lithium as a systemic modulator of bone and brain health through shared molecular pathways. This review examines the molecular basis, preclinical data, and clinical observations suggesting that lithium-long established as first-line therapy for bipolar disorder-may simultaneously protect against osteoporosis and neurodegeneration as two clinical conditions increasingly recognized to share biological substrates. Lithium inhibits glycogen synthase kinase-3β (GSK-3β), stabilizes β-catenin, and activates Wnt signaling in neurons and osteoblasts, while also modulating calcium-inositol homeostasis and suppressing NF-κB-mediated inflammation. Large observational studies report lower dementia incidence and reduced fracture risk in long-term lithium users, together with increases in bone mineral density. Declining brain lithium concentrations in patients with Alzheimer's disease raise the hypothesis that lithium may act as an essential micronutrient rather than solely a pharmacological agent. Bidirectional brain-bone crosstalk involving osteocalcin signaling and sclerostin transport across the blood-brain barrier provides a mechanistic basis for these pleiotropic effects. Lithium offers a unique paradigm for understanding and potentially treating age-related decline in multiple organ systems at subclinical dosage and concentration. However, observational study limitations, optimal dose uncertainties, and toxicity related to long-term usage concerns necessitate rigorous randomized controlled trials before broader clinical recommendations can be made. Future research should focus on optimizing formulation and patient selection to realize lithium's dual protective potential for bone and brain while minimizing risk.
PURPOSE OF REVIEW: The female sex is itself a major risk factor for both osteoporosis and Alzheimer’s disease (AD), two age–related, chronic conditions that rise sharply during the menopausal transition. Although estrogen deficiency has traditionally been viewed as the primary cause of female predominance of postmenopausal bone loss and cognitive decline, emerging evidence suggests that rising follicle–stimulating hormone (FSH) levels, particularly during late perimenopause and beyond, play an independent and critical role. This Review will summarize the direct effect of FSH on the skeleton and brain. RECENT FINDINGS: Large epidemiologic studies have shown that elevated serum FSH levels correlate with negative skeletal consequences, even after adjustment for estrogen. Pre–clinical studies demonstrate that FSH directly activates osteoclasts to promote bone resorption and suppresses osteoblastogenesis. Findings in Alzheimer’s disease mouse models likewise reveal that FSH binds to neuronal FSH receptors in AD–prone brain regions and accelerates amyloid and tau pathology. Population studies support these mechanistic insights by linking rising FSH levels to cognitive decline. This corpus of evidence has not only reframed FSH as an aging hormone that affects both the skeleton and brain, but also reveals a new therapeutic avenue that includes the development of FSH blocking antibodies to address multiple age–related diseases that disproportionately affect postmenopausal women.
PURPOSE OF REVIEW: While GWAS has identified many loci associated with bone mineral density (BMD), translating these findings into functional insights and treatments remains challenging. Post-GWAS methods such as Transcriptome-Wide Association Study (TWAS), Phenome-Wide Association Study (PheWAS), and Mendelian Randomization (MR) provide complementary strategies to prioritize genes and causal risk factors. This review summarizes findings from these studies. RECENT FINDINGS: TWASs have identified many potential causal genes for BMD, but only a few, such as PPP6R3, have been confirmed through functional validation. Several MR studies have provided increasing evidence of causal relationships between inflammatory bowel disease, NAFLD, COPD, and lower BMD, along with a higher risk of osteoporosis. PheWAS and MR also identify bone marrow fat as a risk factor for decreased BMD. It is essential to bridge the critical gap between statistical discovery and biological validation. Moreover, the lack of bone-specific transcriptomic data remains a significant limitation, underscoring the need to generate such datasets. At the same time, all MR evidence should be corroborated with other sources to strengthen causal conclusions.
Naringenin is a plant-derived flavonoid having anti-proliferative, anti-inflammatory, and anti-angiogenic properties against various metabolic disorders. Though there are reports demonstrating the osteogenic potential of naringenin, its effect remains largely unexplored in senile osteoporosis. The current study was planned with the objective to demonstrate the osteoprotective effect of naringenin in conditions of senile osteoporosis induced by d-galactose (D-gal). The results in the d-gal aging bone loss animal model suggest that naringenin improves bone microarchitecture, promotes ex-vivo mineralization, and alters bone serum markers. To check the mode of action of naringenin behind its protective effect, further experiments were performed at the cellular level. Naringenin facilitates osteoblast differentiation and suppresses osteoblast senescence, apoptosis, and cellular reactive oxygen species production in primary osteoblast cells after d-gal stimulation. Mechanistically, naringenin mitigates senescence through the estrogen receptor-mediated pathway, as confirmed when calvarial osteoblast cells treated with ICI182.780, an estrogen pathway inhibitor, greatly decrease its effectiveness. Taken together, these results lead us to conclude that naringenin may function as a potential therapeutic agent for senile osteoporosis.
Anaemia and bone disease commonly co-exist, particularly in chronic conditions such as haemoglobinopathies and chronic kidney disease. The effects on bone are mediated by multiple factors, including marrow expansion, iron overload, endocrine dysfunction, and disruptions in mineral metabolism. These changes compromise bone strength, increasing the risk of osteoporosis and fractures. Although therapeutic advances such as iron infusion and chelation therapy have significantly improved the management of anaemia and patient outcomes, their effects on bone health are often under-recognised with osteoporosis detection occurring after a fracture. Furthermore, with denosumab being a popular anti-resorptive choice amongst clinicians, an emerging and under-appreciated complication is the increasing number of case reports describing hypophosphataemia associated with concurrent anti-resorptive and parenteral iron. This review discusses the bi-directional relationship between anaemia and bone metabolism. By focusing on the central role of fibroblast growth factor-23 (FGF-23), as a link between anaemia, phosphate regulation, and bone metabolism, this review draws attention to under-recognised skeletal risks. Importantly, it offers practical recommendations for monitoring, bridging mechanistic insights with clinical practice where current guidelines remain limited.
Osteosarcopenia, defined as the coexistence of osteoporosis and sarcopenia, is an emerging geriatric syndrome linked to the musculoskeletal decline associated with aging. It is correlated with an increased risk of falls, fractures, disability, and mortality. This review aims to synthesize the emerging concepts, underlying mechanisms, epidemiology, diagnostic challenges, and current therapeutic strategies for osteosarcopenia. A narrative review was conducted using the PubMed, Scopus, and Google Scholar databases. The keywords used were: osteosarcopenia, sarcopenia, osteoporosis, frailty, and related terms. Relevant peer-reviewed studies and reports from international organizations were included. The selected articles, addressing definitions, pathophysiology, epidemiology, diagnosis, and management, underwent thematic analysis. Osteosarcopenia affects approximately 18% to 20% of older adults. Its prevalence increases with age and is higher in women. Osteosarcopenia results from mechanisms common to both bones and muscles, including chronic inflammation, hormonal decline, genetic and epigenetic factors, dysregulated signaling pathways, and the interplay between muscles and bones. Risk factors include age, sedentary lifestyle, malnutrition, chronic diseases, and endocrine disorders. Diagnosis remains complex due to the lack of standardized criteria and relies on separate assessments such as bone densitometry (DXA) for bone density and functional tests for muscle strength. The emergence of biomarkers and composite indices holds promise for improved detection. Management primarily involves resistance training, nutritional optimization (protein, calcium, vitamin D), and anti-osteoporosis medications. However, no treatment simultaneously targets both components, and pharmacological options remain limited. Osteosarcopenia represents a major and growing public health problem in aging populations. Despite progress in understanding its pathophysiology, gaps persist in standardized diagnosis and integrated treatment. Multidisciplinary approaches combining physical exercise, nutrition, and pharmacotherapy, as well as future research on unified diagnostic criteria and targeted therapies, are essential to reduce its impact and improve the functional abilities of older adults.
Pinellia ternata (Thunb.) Breit. has been used in China for more than two thousand years to treat cough and vomiting. P. ternata is rich in polysaccharides; however, current research on the bioactivity of polysaccharides from P. ternata is relatively limited. In particular, there are no reports on their application in the treatment of osteoporosis. In this study, two β-glucan-like polysaccharides were isolated from P. ternata. The primary structures of PTTP50-1-3 and PTTP50-1-4 were comprehensively analyzed using high performance liquid chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance. The results indicated that they possess a similar backbone structure. Notably, compared with PTTP50-1-3, PTTP50-1-4 exhibits characteristics of more branching and higher β-glucan content, as well as lower molecular weight. In vitro experiments demonstrated that both PTTP50-1-3 and PTTP50-1-4 could increase the alkaline phosphatase activity of osteoblastic MC3T3-E1 cells. In addition, PTTP50-1-4 was able to enhance the mineralization of MC3T3-E1 cells by upregulating the expression of Runx2, Osx, Bmp2, Ocn, Opn, and Bsp. These findings suggest that P. ternata polysaccharides with a β-glucan-like structure may possess strong anti-osteoporotic potential, which provide a theoretical foundation for further research and development of P. ternata polysaccharides in the prevention and treatment of osteoporosis.
Studies have shown that there are a lot of risk factors that could cause periprosthetic osteolysis and aseptic loosening, threatening the life-span of the hip prosthesis. Breast cancer is one of the most frequent malignancy in women. However, the use of breast cancer chemotherapy and hormonal therapy has been shown to significantly elevate the risk of osteoporosis. Chemotherapy can systematically suppress the anabolism of various organs, ultimately leading to bone metabolism dysfunction and osteolysis. Aromatase inhibitors (AI) function by inhibiting the conversion of androgens to estrogen, thereby reducing systemic estrogen levels, which is essential for maintaining bone mass; however, prolonged estrogen deprivation can lead to osteoporosis, which has been proven to pose a significant threat to the survival of hip implants. In this case, the patient suffered hip joint tuberculosis and took intertrochanteric osteotomy procedure at age 24. Seventeen years after, she took Total Hip Arthroplasty (THA). She then undertook chemotherapy and hormonal therapy for breast invasive ductal carcinoma (BI-RADS category III), 1 year after her primary THA. Three years later, she was diagnosed with aseptic loosening of her hip prosthesis. A summary and analysis of her treatment were conducted. Breast cancer chemotherapy and hormonal therapy might be a threat to the stability of THA prosthesis. More attention should be paid when a Total Hip Arthroplasty patient received chemotherapy and hormonal therapy. Further research is needed to fully understand the impact of breast cancer treatments, as current therapies like hormonal therapy can increase the risk of osteoporosis and fractures.
In 2024, the National Academies of Sciences, Engineering, and Medicine (NASEM) published a report entitled Advancing Research on Chronic Conditions in Women. A major purpose of this report was to summarize the current state of research into a series of 21 chronic conditions that affect women differently or that are more common in women. The American Society for Bone and Mineral Research (ASBMR) established a working group to evaluate the NASEM report's implications for women's MSK health. This perspective summarizes key research gaps identified in the NASEM report, including the lack of sex-specific data, underrepresentation of women in clinical studies, and minimal integration of MSK health with other chronic conditions. The NASEM report underscores the need for more comprehensive study designs that consider hormonal, genetic, and social determinants of health across the lifespan. In addition to osteoporosis, in this perspective, the ASBMR working group highlights emerging but poorly understood evidence of detrimental effects on musculoskeletal biology in non-MSK, chronic diseases that were identified in the NASEM report to disproportionately affect women. To advance the field, we advocate for better diagnostics, increased investment, and stronger representation of women in research studies. Addressing these gaps is critical for improving prevention, care, and outcomes for chronic conditions that uniquely or disproportionately affect women. Chronic health conditions affect women more than men, but past research has often overlooked this fact. In 2024, a national report highlighted how chronic conditions like osteoporosis, back pain and arthritis in women are underfunded and poorly understood. In response, a group from the American Society for Bone and Mineral Research reviewed the report to focus specifically on women’s musculoskeletal health. The report found that women are often not included in clinical studies, and that links between musculoskeletal health and many chronic conditions that impact women’s daily lives, including endometriosis and depression, have not been adequately investigated. In addition, reproductive transitions, such as menopause, are often associated with musculoskeletal symptoms and conditions in addition to osteoporosis, that are poorly understood. Musculoskeletal conditions often start early and last a lifetime, affecting mobility, pain levels, and quality of life. Yet, tools to diagnose, treat, and prevent these chronic conditions are limited. We believe research must do a better job reflecting women’s unique biology and life experiences. This includes ensuring that study participants are representative of the population, identifying better ways to track health over time, and improving access to care. As mobility is central to overall health and disease prevention, we believe that investing in women’s health research—especially in musculoskeletal health—can lead to earlier diagnosis, more effective treatments, cost savings and better lives for millions of women.
Medication-related osteonecrosis of the jaw (MRONJ) is a rare but clinically important adverse event in antiresorptive osteoporosis care. The most recently approved osteoporosis medication, romosozumab, has a dual mechanism, combining antiresorptive and osteoanabolic effects. Thus, concern exists regarding a possible risk for MRONJ with romosozumab, although current evidence is limited mainly to isolated case reports. We performed a retrospective new-user active comparator propensity score-matched cohort study in the TriNetX Global Collaborative Network comparing women treated with romosozumab vs. parathyroid hormone (PTH) analogs (teriparatide or abaloparatide). Women aged ≥ 18 years with no prior osteonecrosis, jaw inflammatory disease, oral/head-neck cancer, or radiation exposure and no recent exposure to chemotherapy were eligible. After 1:1 propensity score matching, 15,689 patients remained in each cohort. During 1 year of follow-up, MRONJ occurred in 11 romosozumab-treated patients and 12 PTH analog-treated patients (hazard ratio [HR] 0.89, 95% CI 0.39-2.01; log-rank p = 0.78). Absolute event rates were very low in both groups (0.070% vs. 0.076%). As expected, the positive control outcome of hypercalcemia occurred less often with romosozumab (HR 0.66, 95% CI 0.58-0.75). These real-world data do not indicate a detectable excess short-term MRONJ risk with romosozumab compared with PTH analogs over the approved treatment window, although modest differences cannot be excluded because events were rare.
Oral corticosteroids (OCSs) are recommended as first-line therapy for sarcoidosis, yet limited data describe the risk of steroid-associated adverse effects in this population. What are the short-term and long-term effects of OCS exposure in terms of developing steroid-related comorbidities in a multinational cohort with sarcoidosis? An electronic questionnaire was codeveloped and translated by an international team of sarcoidosis experts and patients from the United States and Europe. We used inverse probability weighting to estimate the average treatment effect on the treated adjusted for markers of disease severity. Before data collection, we prespecified 2 primary outcomes: (1) development of 13 steroid-associated comorbidities and (2) total weight change. Outcomes were compared across patients with OCS exposure categorized as current, past, or never. We collected self-reported questionnaires from 1,937 patients with sarcoidosis representing 34 countries. In weighted analyses, ever use of OCSs (current or past OCS use) was associated with development of 1.3 more comorbidities (95% CI, 0.8-1.9) compared with never using OCSs. Ever use of OCSs was associated with increased odds for the development of mood changes (OR, 2.1; 95% CI, 1.3-3.4), gastroesophageal reflux disease (OR, 2.3; 95% CI, 1.3-4.1), bruising (OR, 2.3; 95% CI, 1.3-4.1), osteoporosis (OR, 3.8; 95% CI, 1.8-8.1), hyperlipidemia (OR, 1.9; 95% CI, 1.04-3.5), infections (OR, 2.1; 95% CI, 1.1-4.0), and diabetes (OR, 2.7; 95% CI, 1.2-6.0). Ever use of OCSs was associated with 5.9 kg (95% CI, 3.8-8.0 kg) more net weight gain than never use. The effects of OCS use were more pronounced between ever and never OCS users and were similar between current and past OCS users. Ever use of OCSs was associated with multiple steroid-related comorbidities and weight gain in patients with sarcoidosis. Notably, adverse effects persisted even after OCS discontinuation.
Osteoporotic fractures remain a major cause of morbidity and mortality worldwide. Current clinical assessment metrics (e.g., bone mineral density) are limited in their ability to identify fracture risk and bone strength. Statistical Shape and Appearance Modelling (SSAM) offers a method to quantify anatomical geometry and density patterns. This review examines advancements in SSAM for osteoporosis research. Recent literature demonstrates that SSAM can capture detailed bone geometry and internal density distribution. Increasingly, these models are combined with computational analytics, including finite element analysis and machine learning, to assess the mechanical and structural behavior of bone. SSAM provides a robust quantitative framework for bone research. Notably, SSAM is used to reconstruct 3D subjects from clinical 2D images for biomechanical evaluation. Although clinical adoption remains limited by generalizability, the advancement of deep learning and complex SSAM pipelines supports its potential for osteoporosis screening and fracture risk prediction.