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Obesity and its associated comorbidities constitute a serious and growing public health burden. Fractures affect a substantial proportion of people with obesity and result from reduced bone strength relative to increased mechanical loading, together with an increased risk of falls. Factors contributing to fractures in people with obesity include adverse effects of adipose tissue on bone and muscle and, in many people, the coexistence of type 2 diabetes. Strategies to reduce weight include calorie-restricted diets, exercise, bariatric surgery, and pharmacological interventions with GLP-1 receptor agonists. However, although weight loss in people with obesity has many health benefits, it can also have adverse skeletal effects, with increased bone loss and fracture risk. Priorities for future research include the development of effective approaches to reduce fracture risk in people with obesity and the investigation of the effects of GLP-1 receptor agonists on bone loss resulting from weight reduction., Competing Interests: Declaration of interests JP reports consulting fees from Kyowa Kirin, Eli Lilly, and Theramex; honoraria from Amgen, Besins, CDD Laboratoire de la Femme, Kyowa Kirin, and Theramax; payment for expert testimony from UCB; and support for attending meetings from Kyowa Kirin and Theramax. JEC reports consulting fees from Boehringer-Ingelheim and Alkem; honoraria from Amgen; and payment for expert testimony from Gilead., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Context: Bone marrow adiposity (BMAT) alterations in patients with type 2 diabetes mellitus (T2DM) may contribute to adverse bone effects., Objective: Characterization of BMAT content and composition in patients with well-controlled T2DM., Methods: This cross-sectional study included 2 groups of postmenopausal women: one with T2DM and the other without. The proton density fat fraction (PDFF) of the lumbar spine and proximal femur, comprising the femoral head, neck, and diaphysis, was assessed using chemical shift-based water-fat separation imaging (WFI). Magnetic resonance imaging with spectroscopy ( 1 H-MRS) was performed in a subgroup of participants to confirm the PDFF measurements and determine the apparent lipid unsaturation level (aLUL) at the L3 vertebrae and femoral neck. The association of imaging-based PDFFs and aLUL between diabetes groups was investigated by adjusting for confounding factors using a linear mixed model., Results: Among 199 participants, patients with T2DM (n = 29) were significantly heavier ( P < .001) and had a higher bone mineral density (BMD) ( P < .001 for all sites) than nondiabetic patients (n = 170). When PDFFs were compared after adjusting for age, body mass index (BMI), and BMD, the femoral head WFI-based PDFF was lower in patients with T2DM (mean [standard error] 88.0% [0.7] vs 90.6% [0.3], P < .001). Moreover, the aLUL at the L3 vertebrae was lower in patients with T2DM (n = 16) than in without (n = 97) (mean [standard error] 3.9% [0.1] vs 4.3% [0.1], P = .02)., Conclusion: The content and composition of BMAT are modified in postmenopausal women with T2DM and these changes occur at specific sites., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Importance: Osteoporotic vertebral compression fractures (VCFs) frequently cause substantial pain and reduced mobility, posing a major health problem. Despite the critical need for effective pain management to restore functionality and improve patient outcomes, the value of various conservative treatments for acute VCF has not been systematically investigated., Objective: To assess and compare different conservative treatment options in managing acute pain related to VCF., Data Sources: On May 16, 2023, 4 databases-PubMed, Embase, Scopus, and CINAHL-were searched. In addition, a gray literature search within Scopus and Embase was also conducted., Study Selection: Included studies were prospective comparative and randomized clinical trials that assessed conservative treatments for acute VCF., Data Extraction and Synthesis: Data extraction and synthesis were performed by 2 authors according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analyses recommendations. A frequentist graph-theoretical model and a random-effects model were applied for the meta-analysis., Main Outcomes and Measures: Primary outcomes were short-term (4 weeks) pain during activity and long-term (latest available follow-up) nonspecified pain in patients with acute VCF., Results: The study included 20 trials, encompassing 2102 patients, and evaluated various interventions for managing VCF. Calcitonin (standardized mean difference [SMD], -4.86; 95% CI, -6.87 to -2.86) and nonsteroidal anti-inflammatory drugs (NSAIDs; SMD, -3.94; 95% CI, -7.30 to -0.58) were beneficial regarding short-term pain during activity compared with placebo. For long-term nonspecific pain management, bisphosphonates were associated with inferior pain outcomes compared with daily (SMD, 1.21; 95% CI, 0.11 to 2.31) or weekly (SMD, 1.13; 95% CI, 0.05 to 2.21) administration of teriparatide, with no treatment being superior to NSAIDs. The qualitative analysis of adverse events highlighted that typical adverse events associated with these medications were observed., Conclusions and Relevance: NSAIDs and teriparatide may be the preferred treatment options for pain management in acute osteoporotic VCF. Although calcitonin also proved to be beneficial, its safety profile and potential adverse effects restrict its widespread application. The limited evidence on braces and analgesics underscores the urgent need for future research.

Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders; however, concerns have arisen about their prolonged and inappropriate use. Although generally considered safe, recent evidence has linked PPI use with an increased risk of kidney disease, stomach cancer, pneumonia, dementia, cardiovascular events and potential bone health problems. This systematic review examines the effects of PPIs on bone health, including osteoporosis and changes in phosphocalcic and magnesium metabolism, through a comprehensive analysis of the recent literature. The relationship between PPIs, bone mineral density and fracture risk, especially in populations with comorbidities, is complex and we propose a focus based on recent data. Studies of the effect of PPI use on bone mineral density have shown mixed results and require further investigation. Observational studies have indicated an increased risk of fractures, particularly vertebral fractures, associated with PPI use. Recent meta-analyses have confirmed an association between PPI use and hip fractures with a dose-dependent effect. More recently, PPIs have been associated with serious disturbances in phosphocalcic and magnesium metabolism that require careful management and discontinuation. Proton pump inhibitor-induced hypomagnesemia (PPIH) is a well-established phenomenon. In addition, hypocalcemia secondary to severe hypomagnesemia has been described. Despite growing evidence of PPI-related risks, further research is essential to better understand the complex mechanisms, as most data are from observational studies and do not establish a causal relationship. This review emphasizes the need for judicious prescription practices, particularly in long-term use scenarios and rheumatological contexts., (Copyright © 2024 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Osteoanabolic agents are used as a first line treatment in patients at high fracture risk. The PTH receptor 1 (PTH1R) agonists teriparatide (TPTD) and abaloparatide (ABL) increase bone formation, bone mineral density (BMD), and bone strength by activating PTH receptors on osteoblasts. Romosozumab (ROMO), a humanized monoclonal antibody against sclerostin, dramatically but transiently stimulates bone formation and persistently reduces bone resorption. Osteoanabolic agents increase BMD and bone strength while being more effective than antiresorptives in reducing fracture risk in postmenopausal women. However, direct comparisons of the antifracture benefits of osteoanabolic therapies are limited. In a direct comparison of TPTD and ABL, the latter resulted in greater BMD increases at the hip. While no differences in vertebral or non-vertebral fracture risk were observed between the two drugs, ABL led to a greater reduction of major osteoporotic fractures. Adverse event profiles were similar between the two agents except for hypercalcemia, which occurred more often with TPTD. No direct comparisons of fracture risk reduction between ROMO and the PTH1R agonists exist. Individual studies have shown greater increases in BMD and bone strength with ROMO compared with TPTD in treatment-naive women and in women previously treated with bisphosphonates. Some safety aspects, such as a history of tumor precluding the use of PTH1R agonists, and a history of major cardiovascular events precluding the use of ROMO, should also be considered when choosing between these agents. Finally, convenience of administration, reimbursement by national health systems and length of clinical experience may influence patient choice., Competing Interests: Conflict of interest: Athanasios D. Anastasilakis reports lecture fees from Amgen, Bianex, Eli-Lilly, Galenica, ITF, Unifarma, and UCB; Maria P. Yavropoulou reports lecture fees from Amgen, Galenica and Genesis; Andrea Palermo reports lecture fees from Amgen, Theramex and UCB; Polyzois Makras reports fees for lectures/advisory boards and research grants from Amgen and Galenica and fees for lectures/advisory boards from UCB, Elpen, Bianex, Eli-Lilly, ITF, Unipharma, and Rapharm; Julien Paccou reports honoraria for lectures/advisory boards from Amgen, Besins, CDD, Lilly, UCB, and Theramex; Gaia Tabacco reports lectures fees from Theramex and Abiogen, Anda M. Naciu reports lecture fees from Theramex; Elena Tsourdi reports honoraria for lectures and advisory boards from Amgen, UCB, Ascendis, Kyowa Kirin, and educational grants from Ascendis and UCB. Co-authors Elena Tsourdi is on the editorial board of EJE. She was not involved in the review or editorial process for this paper, on which she is listed as an author., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We used data from a Fracture Liaison Service to compare the mean T-scores of obese and non-obese patients after a recent fragility fracture. After adjusting for age, sex, and diabetes mellitus, T-score values were significantly higher at all measurement sites in obese patients, with a mean difference of 1 SD., Purpose: This study aimed to compare the mean T-scores of obese and non-obese patients after recent fragility fractures., Methods: Over a period of 5 and a half years, from January 2016 to May 2021, patients from a fracture liaison service were identified and their demographic characteristics, osteoporosis risk factors, BMD T-scores, and fracture sites were compared between obese (BMI ≥ 30 kg/m 2 ) and non-obese (19 kg/m 2  < BMI < 30 kg/m 2 ) patients., Results: A total of 712 patients were included (80.1% women; mean age 73.8 ± 11.3 years). Sixteen % had type 2 diabetes mellitus and 80% had a major osteoporotic fracture (MOF). 135 patients were obese and 577 non-obese, with obese patients younger (p < 0.001) and more frequently female (p = 0.03). Obese patients presented with fewer hip fractures (10% vs. 21%, p = 0.003) and more proximal humerus fractures (16% vs. 7%, p < 0.001) than non-obese patients. After adjusting for age, sex, and diabetes mellitus, BMD T-score values were significantly higher at all measurement sites (lumbar spine, total hip, and femoral neck) in obese patients than in non-obese patients for all types of fractures, with a mean difference of 1 standard deviation (p < 0.001 for all comparisons). The same results were observed in the population limited to MOF., Conclusions: Given the crucial role of BMD T-score in determining the need for anti-osteoporotic medication following fragility fractures, it is reasonable to question the existing T-score thresholds in obese patients., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Few studies on the risk of incident major adverse cardiac and cerebrovascular events (MACCEs) in sarcopenia have been reported. The objective was to assess the association between presarcopenia and sarcopenia and a higher risk of MACCEs., Methods: This study on the UK Biobank prospective cohort, used data collected between 2006 and 2021. Community-dwelling Caucasian participants aged 37 to 73 years were included if values for Handgrip Strength (HGS) and Skeletal Muscle Index (SMI) were available and if no history of MACCEs was reported. Exposure was assessed using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Muscle strength was measured using HGS, and muscle mass using the SMI. Presarcopenia was defined through the two definitions available in the literature, as low HGS with normal SMI and as normal HGS with low SMI, whereas sarcopenia was defined as low HGS with low SMI. The main outcome was to determine whether presarcopenia and/or sarcopenia were predictors of MACCEs (composite events)., Results: A total of 406,411 included participants (women: 55.7%) were included. At baseline, there were 18,257 (4.7%) presarcopenics-subgroup n°1 (low HGS only), 7940 (2.1%) presarcopenics-subgroup n°2 (low SMI only), and 1124 (0.3%) sarcopenics. Over a median follow-up of 12.1 years (IQR: [11.4; 12.8]), 28,300 participants (7.0%) were diagnosed with at least one event. Compared to NonSarc, presarcopenic (subgroups n°1 and n°2) and sarcopenic status were significantly associated with a higher risk of MACCEs (respectively fully adjusted HRs: HR = 1.25 [95% CI: 1.19; 1.31], HR = 1.33 [95% CI: 1.23; 1.45] and HR = 1.62 [95% CI: 1.34; 1.95])., Conclusions: In a community-dwelling population, the risk of MACCEs was higher in both presarcopenic and sarcopenic participants., (© 2023 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Objective: The EULAR task force recently published the difficult-to-treat RA (D2T RA) definition, however, a definition of D2T axSpA is still lacking and limitations in this definition exist. The objectives were to study the characteristics of D2T axSpA patients using the EULAR definition and to study a subgroup of patients with a predefined more stringent definition including a temporal criterion., Methods: A multicentric retrospective study was performed. D2T axSpA was defined as failure of≥2 b/tsDMARDs with different mechanism of action. Very D2T axSpA was defined as failure of≥2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T axSpA patients were compared to non-D2T (nD2T) axSpA patients., Results: Three hundred and eleven axSpA patients were included: 88 D2T axSpA (28.3%) and 223 non-D2T (nD2T) axSpA (71.7%). Peripheral involvement was more prevalent in the D2T group (34.9 vs. 21.4%; P=0.015). BASDAI level at baseline was higher in the D2T group (63.7±16.5 vs. 58.8±14.7; P=0.015). Fibromyalgia was found to be more frequent in the D2T group vs nD2T group (P<0.001). Twelve patients (3.8%) were categorized as very D2T axSpA. Compared to nD2T, Very D2T patients had a higher CRP level at baseline (42.0±31.3 vs. 17.8±23.1; P=0.010). IBD prevalence at baseline was higher in the very D2T group (41.7 vs. 3.1%; P<0.001). None of the very D2T patients presented a fibromyalgia., Conclusion: D2T axSpA was associated with higher disease activity, peripheral involvement, extra-musculoskeletal manifestations and fibromyalgia. Very D2T patients represented a minim proportion of patients after applying a more stringent definition including a temporal criterion of 2 years and might be independent from fibromyalgia., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)