Fibrous dysplasia/McCune-Albright (FD/MAS) syndrome is a rare bone disorder with a broad clinical manifestation. Pain is the most frequently reported complaint and can significantly impair quality of life. While most existing data are cross-sectional, little is known about symptom progression over time. This study aimed to assess changes in pain and QoL over 2 years follow-up. Patients in the PROFID study completed yearly questionnaires aligned with check-ups or independently if check-ups were less frequent. At baseline, 143 (85.6%) reported pain, of which 38 (26.6%) mild, 105 (73.4%) moderate/severe pain, and 24 (14.4%) had no pain. Emotional wellbeing and energy/fatigue were the most affected in the SF-36 domains. Patients viewed their disease as chronic, with moderate daily fluctuation and impact showed that active and palliative coping were the most frequently used coping mechanism. After 2 years, 27.4% of those with no or mild pain at baseline reported a significant increase in pain (1.3-5.0, p < 0.001), while scores in the moderate/severe group remained stable (6.6-6.3, p = 0.5). Emotional wellbeing improved significantly (37.6-55.5, p < 0.001). Patients with moderate/severe pain reported increased disease control, whereas those with no/mild pain felt less control (p = 0.01). Higher pain scores correlated with poorer physical (r = - 0.627), social (r = - 0.541), and general health (r = - 0.452), worse illness perceptions (e.g., illness identity r = 0.3), and greater palliative coping (r = 0.4), all p < 0.05. These findings emphasize the need to address both physical and psychological aspects of FD/MAS.

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and occurs in both high- and low-turnover bone disorders. While phosphate (P) control is known to reduce adverse effects, most supporting studies have focused on high-turnover models. This study evaluates the effects of two P binders-calcium carbonate (CaCO₃) and sevelamer carbonate-on laboratorial markers and bone histomorphometry in a low-turnover bone disease model. Wistar rats underwent 5/6 nephrectomy and total parathyroidectomy (Nx + PTx) to induce low-turnover bone disease. Animals were assigned to 4 groups: Sham, untreated Nx + PTx, Nx + PTx + CaCO₃, and Nx + PTx + sevelamer. After 8 weeks, we performed biochemical analysis, bone histomorphometry, gene expression (SOST, β-catenin, DKK-1), immunohistochemistry (sclerostin, β-catenin, FGF23, DKK-1), and apoptosis assays. Bone histology confirmed low-turnover disease in Nx + PTx rats, which also developed CKD and hyperphosphatemia. Both P binders effectively reduced serum P levels, but only CaCO₃ corrected hypocalcemia. Notably, CaCO₃ treatment led to increased osteoid parameters, elevated osteoblast surface and absence of tetracycline labeling - hallmarks of osteomalacia. Moreover, CaCO₃ increased osteoblast apoptosis. In a rat model of low-turnover bone disease with normal dietary P, high-dose CaCO₃ impaired bone mineralization and induced osteomalacia. These findings highlight potential risks of calcium-based phosphate binders in patients with low bone turnover and hyperphosphatemia, supporting the need for careful clinical consideration and monitoring.

Opportunistic chest CT (OC-CT) presents significant potential for early osteoporosis screening. However, its application remains limited to specific patient populations, and the optimal vertebral level for osteoporosis detection has yet to be determined. This study aimed to determine the optimal vertebral level and assess the feasibility of OC-CT, with dual-energy X-ray absorptiometry (DXA) being the gold standard. We retrospectively included 1236 participants aged 50 years or above and who completed both DXA and routine chest CT scans within 6 months. Receiver operation characteristic (ROC) analysis was used to evaluate the diagnostic performance in detecting low bone mass and osteoporosis. Among 15,007 vertebrae analyzed, CT at the 1st-12th thoracic (T1-T12) and the 1st lumbar (L1) vertebrae exhibited good discrimination for low bone loss and osteoporosis with the area under the ROC curve exceeding 0.80. Notably, T8 was the only vertebra to achieve sensitivity above 0.80 for both conditions: a cut-off value of 163.5 Hu yielded 81% sensitivity and 84% specificity for low bone mass, while 132.3 Hu yielded 82% sensitivity and 75% specificity for osteoporosis. These findings indicated that OC-CT demonstrated comparable diagnostic performance to DXA for bone mass evaluation in individuals aged 50 years or above. T8 was recommended as the optimal vertebral level for opportunistic bone mass evaluation, and T7 and T10 vertebrae were the preferred alternatives when T8 was not available. We also provided a user-friendly self-check table for rapid bone mass evaluation to facilitate clinical utility.

Meclizine has been shown to promote bone growth by inhibiting a key signaling pathway involved in achondroplasia (ACH). Earlier studies demonstrated its safety in children with ACH after short-term use. The purpose of this study is to assess the safety and efficacy of meclizine treatment over 26 weeks in children with ACH. This open-label, single-arm, Phase 2 study was conducted at four sites in Japan. Nine children with ACH, aged 5-10 years old, received daily meclizine (12.5 mg/day for those < 20 kg; 25 mg/day for those ≥ 20 kg). This was co-administered with growth hormone therapy for 26 weeks. Safety was monitored through adverse events (AEs), while treatment efficacy was measured by changes in height velocity (cm/year). Secondary measures included the proportion of children achieving a height velocity of ≥ 6 cm/year and changes in arm span growth. Arm span velocity and the proportion of participants reaching ≥ 6 cm/year were evaluated through ad hoc analyses. No serious AEs were reported. Height velocity increased slightly from 4.35 ± 1.36 cm/year pre-treatment to 4.46 ± 1.54 cm/year post-treatment. One participant achieved a height velocity of ≥ 6 cm/year. Mean height increased from 107.48 ± 9.04 to 109.77 ± 8.69 cm over the study period. By contrast, arm span velocity was higher at 6.93 ± 2.50 cm/year, with six children reaching ≥ 6 cm/year. An additive effect of meclizine and growth hormone on promoting height was not observed; however, meclizine may enhance arm span growth in children with ACH.Trial registration number jRCT2041230001.

Sarcopenia, characterized by progressive loss of muscle mass, strength, and function, significantly impacts patient outcomes. Accurate assessment of muscle mass is essential for its diagnosis. Currently the agreement on how to use imaging for sarcopenia detection is still debated and how well the muscle imaging assessments correlate with muscle function needs further agreement. Recognizing the critical role of imaging in this process, the China National Center for Orthopedics (NCO) and the East Meets West Action Group of European Calcified Tissue Society (ECTS) convened a working group endorsed by the Board of the ECTS. This paper aims to evaluate the utility of various imaging techniques for diagnosing sarcopenia and understanding its functional consequences. We synthesize evidence on DXA, BIA, CT, MRI and ultrasound, and provide specific related recommendations. Imaging cannot replace functional assessments, but may enhance them by revealing subclinical disease, clarifying pathophysiology, and enabling individualized care. We hope to assist clinicians and researchers in using imaging to improve sarcopenia diagnosis, prognosis, and therapeutic monitoring, while also advocating for evidence-based structural and functional criteria in future guidelines.

Axial spondyloarthritis (axSpA) is a chronic inflammation disorder commonly associated with osteoporosis and fractures. For further information about the pathophysiology of the latter, we analyzed transiliac biopsy samples from n = 21 men with axSpA (age 46 ± 6 years, mean ± SD). This cohort comprised patients with (GROUP-1, n = 5) or without increased osteoid thickness and mineralization lag time by histology (GROUP-2, n = 16). We performed quantitative backscattered electron imaging for bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS), and Raman microspectroscopy for bone material/compositional properties in cancellous (Cn.) and cortical (Ct.) bone compartments. Patients' outcomes were compared to different respective reference (REF)/control (CTRL) data. The total cohort and subgroup GROUP-1 (considered separately) showed significant deviations in BMDD versus REF. The average degree of cancellous bone mineralization was decreased by - 1.8% (p < 0.05) in the total cohort and decreased by - 5.1% (p < 0.01) in GROUP-1, while GROUP-2 had normal BMDD. The total cohort and both subgroups showed abnormal osteocyte OLS-characteristics. Specifically, the respective increases in OLS-area in cancellous and cortical bone were + 14.4% and + 44.5% in GROUP-1 and + 8.8% and + 24.9% in GROUP-2. The total cohort as well as both subgroups showed additionally deviations in organic matrix properties from CTRL with an increased pyridinoline content versus CTRL in both the cohort and subgroups. Our findings showed abnormal bone matrix mineralization in these patients with axSpA, with the largest deviations in the subgroup with histologically defined mineralization defects. The also observed altered osteocyte morphology and pyridinoline content might suggest osteocyte and osteoblast functional abnormalities in axSpA.

Follicle-stimulating hormone (FSH) was independently associated with lumbar spine (LS) bone mineral density (BMD), while estradiol (E2) predicted femoral neck BMD. A threshold effect for FSH (~ 15 mIU/mL) suggests site-specific and non-linear hormonal influences on bone during the menopausal transition. To investigate the association between serum FSH levels and BMD in midlife women, and to determine whether these associations persist after adjustment for E2 and age, with particular attention to site-specific effects. We conducted a cross-sectional study of 224 women aged 45-60 years, selected from an institutional database. Inclusion required simultaneous measurements of serum FSH, E2, and BMD at the LS, femoral neck (FN), and total hip (TH) by dual-energy X-ray absorptiometry. Women using anti-osteoporotic drugs, hormone therapy, or medications affecting bone, were excluded. Analyses included non-parametric tests, Spearman's correlations, multivariable linear regression with log-transformed hormones and stepwise BIC selection, and segmented regression. FSH rose progressively across menopausal stages, while E2 declined,, paralleling lower BMD values. Higher FSH correlated inversely with LS (ρ = -0.26, p < 0.001) and FN-BMD (ρ = -0.29, p = 0.041), while E2 correlated positively with LS-BMD (ρ = 0.22, p = 0.018). In multivariable models, log-FSH remained independently associated with LS-BMD (β = -0.072, p = 0.009), whereas log-E2 was the only predictor at FN-BMD (β = 0.138, p = 0.020). No predictors were retained for TH-BMD. Segmented regression identified a breakpoint at ~ 15 mIU/mL of FSH, below which LS-BMD declined steeply (β = -0.007 g/cm per mIU/mL), with a plateau thereafter. FSH and E2 exert distinct, site-specific influences on bone. FSH was independently associated with LS-BMD and showed a threshold effect, while E2 was more relevant to FN. These findings suggest that menopausal bone loss is not solely estrogen-driven but also involves gonadotropin-mediated mechanisms.

Osteogenesis imperfecta (OI) is a group of rare, hereditary diseases caused by mutations to the genes involved in the biosynthesis of collagen type 1. A cardinal feature of OI is the frequent occurrence of fractures. Individuals with OI often experience pain that is not related to fracture episodes. However, little is known about the use of analgesics among people with OI. We aim to examine the use of analgesics in Danes with OI as a measure of pain, using register-based data. This study is a Danish nationwide, population-based, and register-based cohort study. It includes all individuals registered with an OI diagnosis from January 1977 to December 2018, and a reference population matched by birth month, year, and sex. We examined the number of prevalent analgesic users over time and by age, the amount of analgesic use in Defined Daily Doses (DDDs), and the risk of initiating analgesics as well as treatment at a specialised pain centre during the observation period. We present the Sub Hazard Ratio (SHR) [95% confidence interval] for the endpoints comparing the OI cohort to the reference population. Lastly, we evaluated the changes in analgesic use related to fractures in the OI cohort and the proportion of long-term opioid users in both cohorts. A total of 905 individuals with OI and 4542 in the reference population were identified. There were more prevalent analgesic users (71.8% vs. 46.8%) in the OI cohort, with the number of users increasing over time and with age. Individuals in the OI cohort were more likely to initiate analgesics (SHR 1.86 [1.68-2.05]) and specialised pain care (SHR 5.8 [3.1-11.0]) than in the reference cohort. The use of analgesics, as measured in total DDDs, increased shortly after a fracture in the OI cohort but normalised to pre-fracture levels within 6 months. A higher proportion of the OI cohort had repeated dispensed prescriptions of opioids compared to the reference population. Individuals with OI are more likely to use analgesics and to use more analgesics-as measured by DDDs-than non-OI individuals.

Methylphenidate (MP) is widely prescribed for attention-deficit/hyperactivity disorder in children and adults. Concerns have emerged regarding its potential effects on bone health, including changes in bone mineral density, fracture risk, and size. However, its effects on skeleton remains controversial. This systematic review and meta-analysis aimed to clarify whether MP administration affects bone health in animal models. Our review was registered with PROSPERO (CRD 42023468466) following PRISMA guidelines. A comprehensive search of MEDLINE, Embase, Scopus, and CINAHL was conducted through May 2025, with no restrictions on year or language. Eight studies from 508 identified articles met the inclusion criteria after full-text screening. These studies compared the effects of different doses of MP on bone morphology, biomechanical properties, microarchitecture, and histomorphometric endpoints in rats' axial and appendicular skeletons. The studies also compared the effects of age at initiation of MP treatment and different durations of MP treatment. Overall, a trend emerged indicating that MP may exert detrimental effects on various bone parameters, particularly in long bones, with age at MP treatment initiation and dose- and duration- dependent responses. Additionally, MP treatment may influence bone tissue directly, through actions on bone cells, and indirectly, through changes in body weight. Meta-analyses revealed significant adverse effects on bone morphology and mechanical properties, especially with higher doses and prolonged exposure. However, the overall risk of bias ranged from unclear to high across included studies, requiring caution in interpretation. The findings emphasize the need for further research into the mechanisms behind MP's impact on bone, including age at MP treatment initiation and treatment duration, dose-response relationships, and sex differences. Better understanding of the metabolic pathways which influence MP's effects on the above endpoints could clarify broader implications of MP use on skeletal health and inform clinical practices.

Type 2 diabetes (T2D) increases the risk of hip fracture, yet its global burden remains poorly quantified. This study assessed the association between T2D and hip fracture and estimated the worldwide T2D-attributable burden from 1990 to 2021, with projections to 2046. We updated a meta-analysis of PubMed, Embase, and Cochrane databases to estimate the pooled risk ratio (RR) for hip fracture in adults aged ≥ 40 with T2D. Combining the pooled RR with T2D prevalence and hip fracture data from the Global Burden of Disease study, we calculated the T2D-attributable population attributable fraction (PAF) and burden. Age-standardized incidence rate (ASIR), years lived with disability rate (ASYR), and average annual percentage change (AAPC) were assessed. Eleven studies (from 11,358 screened) indicated that T2D increased hip fracture risk by 34% (RR 1.34, 95% CI 1.17-1.54). In 2021, 4.70% (2.36-7.34) of incident hip fractures (≈950,200 cases) were attributable to T2D, over four times the 1990 estimate (≈200,180 cases). From 1990 to 2021, ASIR and ASYR rose globally, with the highest rates in high socio-demographic index (SDI) regions, particularly High-income North America. Women and older adults had higher burdens, though increases were faster in men. Projections suggest continued global ASIR (AAPC 0.50%) and ASYR (AAPC 0.07%) growth through 2046. T2D significantly contributes to the global hip fracture burden, especially in high-SDI regions. The persistent sex and age disparities underscore the need for targeted prevention strategies in high-risk populations.

Type H vessels are sensitive markers of bone mass. Platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclast was linked with type H vessel generation. Osteocytes (OCY) have been reported to modulate bone metabolism through neuronal induction and active molecules. This study aimed to characterize effect of osteocyte-derived neuropeptide Y (NPY) on ovariectomy (OVX)-induced bone loss in mice and explore the underlying mechanism. Monocytes/macrophages (Mo) were isolated and induced into preosteoclast. Small interfering RNAs were used to knockdown NPY expression in OCY. The culture medium was harvested. Preosteoclast proliferation and PDGF-BB expression were measured by CCK8 analysis and ELISA respectively. Angiogenesis-related experiments were conducted to evaluate the effects of NPY and PDGF-BB on angiogenesis. Western blotting clarified PI3K/Akt pathway involvement in NPY-mediated angiogenesis. In vivo, OVX mice received cultured medium from OCY with NPY knockdown, NPY or vehicle through bone marrow cavity injection. After 2 months, bone samples were collected for µCT and immunofluorescent analysis. Serum OCN, PDGF-BB and VEGF concentrations were assessed by ELISA. It was found that osteocyte-derived NPY inhibits preosteoclast proliferation and PDGF-BB secretion. Culture medium from NPY-stimulated preosteoclasts suppressed migration and tube formation of human microvascular endothelial cells and this effect was reversed following PDGF-BB treatment. NPY negatively regulates preosteoclast PDGF-BB-induced angiogenesis through PI3K/Akt signaling. Importantly, osteocyte NPY exerted detrimental effects on type H vessel formation and aggravated bone loss in OVX mice. Our study identifies a new mechanism by which osteocyte-derived NPY accelerates OVX-induced bone mass loss via inhibiting PDGF-BB secretion and type H vessel formation.

Public health problems regarding the potential association between Parkinson's disease (PD) and the increased prevalence of osteoporosis have been raised. However, the exact relationship, as well as potential treatment strategies, remains unclear and requires further investigation. Melatonin (MLT) is known for its beneficial effects on bone metabolism and its strong neuroprotective properties. Therefore, this study aimed to evaluate the potential role of MLT in the prevention and treatment of bone loss associated with PD using an hemiparkinsonian rat model induced by the destruction of dopaminergic neurons following intracerebral injection of 6-hydroxydopamine (6-OHDA). Forty male Wistar rats were divided into 5 groups: Control (CTR), 6-OHDA, MLT, 6-OHDA + MLT 1, and 6-OHDA + MLT 15. MLT (20 mg/kg/day) was administered intraperitoneally from Day 1 or Day 15, depending on the group. The effects on locomotor performance, oxidative status, bone structure, collagen accumulation, mineralization and the expression of bone marker proteins and genes were examined. Our results showed that the degeneration of dopaminergic neurons caused by 6-OHDA significantly impaired locomotor performance and induced marked alterations in bone parameters. Early MLT treatment (Day 1) mitigated these bone alterations by preserving structural integrity, enhancing collagen accumulation, and modulating bone marker expression. Importantly, beneficial effects on bone were also observed when MLT was administered later (Day 15), despite the absence of significant improvement in motor deficits. These findings suggest that dopaminergic neuron degeneration can negatively influence bone health and that MLT may exert a direct osteoprotective effect, supporting its possible therapeutic utility in managing bone fragility associated with PD.

Osteogenesis imperfecta (OI) is a rare disorder causing multiple fractures throughout life. No treatment has been shown to reduce the risk of fractures in OI. Here, we present the baseline characteristics of participants in the Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid (TOPaZ) trial. The aim of the trial is to determine whether teriparatide and zoledronic acid are superior to standard care in reducing the risk of clinical fractures.

Tissue engineering creates possibilities for promoting bone regeneration, which can culminate in an ideal therapy for treating bone defects. Considering its tools, especially exosomes (Exos), inferring its efficiency is fundamental for future clinical protocols. Therefore, this research aimed to analyze, through a systematic review, the effectiveness of Exos therapy for regenerating bone. The study followed the PRISMA, and an electronic search for literature was performed until January 2024 to answer the PICO question: Would exosome therapy be effective for bone regeneration? Bone regeneration and cellular and molecular mechanisms were included in primary and secondary outcomes, respectively. The dosage, route of administration, and source cells have also been reported. The risk of bias was investigated according to the criteria of SYRCLE's RoB tool. The meta-analysis was executed using the standardized mean difference for bone mineral density (BMD) and volume ratio bone/whole bone (BV/TV) for cranial bone defects. A total of 3718 were examined, and after applying the eligibility criteria and excluding duplicates, 91 articles were included in the results. All studies demonstrated that Exos were effective in promoting regeneration of bone defects, being superior to the control groups established by each study included in this review, in most cases. The meta-analysis proved the superiority of Exos when BMD and BV/TV were analyzed. An increase in the levels of Runx2, ALP, OCN, OPN, CD31, COL-1, and VEGF, and presence of osteoblasts, M2-type macrophages, and endothelial cells, indicating osteogenic and angiogenic molecular and cellular mechanisms. The mesenchymal stem cells are the most commonly used origin cells. Exos dosage was varied, associated with scaffolds or hydrogels for application in bone defects. The risk of bias identified high scientific evidence for most domains. The Exos therapy is effective for bone regeneration and shows promise for this purpose.

Chronic hepatitis C (CHC) is a risk factor for hepatic osteodystrophy, increasing osteoporosis and fracture risks. While historical pegylated interferon/ribavirin (PEG-IFN/RBV) showed variable bone effects, the newer direct-acting antivirals' (DAAs) impact is less clear. This study compared these antiviral strategies' effects on bone metabolism in CHC patients through two separate analyses. First, we conducted a retrospective analysis of a prospectively collected observational cohort (n = 73) to assess longitudinal bone mineral density (BMD) and bone turnover marker (BTM) changes following PEG-IFN/RBV or DAA therapies. Second, to explore mechanisms, we analyzed two independent, publicly available peripheral blood mononuclear cell (PBMC) transcriptomic cohorts from CHC patients treated with PEG-IFN/RBV (GSE7123, n = 69) or an IFN-free DAA regimen (GSE51699, n = 8). Clinically, PEG-IFN/RBV induced a temporary lumbar spine BMD increase, then a post-treatment decline, and modulated BTMs. DAAs showed minimal BMD/BTM effects. PBMC transcriptomics revealed PEG-IFN/RBV responders showed downregulation of osteoclast precursor (OCP)-related gene sets and concurrent upregulation of osteoblast-related gene sets. DAAs had a minimal impact on these PBMC pathways. These findings demonstrate distinct effects of PEG-IFN/RBV and DAA therapies. PEG-IFN/RBV significantly modulates PBMC gene expression related to bone remodeling, potentially contributing to the complex clinical BMD changes, while DAAs appear largely bone-neutral. This highlights treatment-specific osteoporosis risk and surveillance needs in CHC survivors.

Genome-wide association studies have identified multiple loci associated with bone mineral density, a major determinant of osteoporotic fracture risk. At one such locus, genetic, bioinformatic, and zebrafish knockout data strongly prioritize membrane palmitoylated protein 7 (MPP7) as a candidate gene, although its precise role in bone biology remains poorly defined. MPP7 encodes a member of the p55 Stardust family of membrane-associated guanylate kinase proteins, which are key regulators of epithelial cell polarity and junctional organization. Here, we investigated the functional role of MPP7 in bone biology. We found that MPP7 expression was significantly reduced-by approximately twofold-in bone tissue from osteoporotic patients compared with osteoarthritic patients and non-osteoporotic controls. Furthermore, we generated a CRISPR/Cas9-mediated MPP7 knockout in the human osteosarcoma HOS cell line and demonstrated that MPP7 deletion impairs osteogenic differentiation and completely abrogates mineralization through downregulation of ALPL expression. Knockout cells also displayed altered morphology, suggesting that MPP7 influences osteoblast function via effects on cell polarity and adhesion. Collectively, our findings, together with zebrafish genetic evidence, indicate that MPP7 plays a critical role in osteoblast differentiation and mineralization and may contribute to osteoporosis susceptibility in humans.

To examine the association between birth characteristics and bone mineral density (BMD) and bone mineral content (BMC) in young adults.

Proton-pump inhibitors (PPI) are widely used among older adults and PPI intake has been associated with increased fracture risk. However, their association with bone microarchitecture and strength remains unclear as prior clinical PPI studies were restricted to lower-resolution bone imaging techniques such as DXA. Using high-resolution peripheral computed tomography (HR-pQCT), we prospectively investigated whether long-term PPI use was associated with changes in volumetric bone mineral densities, bone microarchitecture, and strength in older patients. 189 patients aged ≥ 60 years (n = 24 persistent PPI users [p-PPI user], and n = 165 non-PPI users), enrolled as part of a 2-year vitamin D RCT, underwent HR-pQCT scanning of the tibia and radius at 0 and 2 years. Bone volumetric density (vBMD), microarchitectural and strength parameters were computed and adjusted linear regression models without and with adjustments, including age, sex, BMI, and treatment groups, were employed to compare changes between p-PPI users and non-PPI users. At baseline, both groups were comparable with respect to age, vBMDs, bone microarchitecture, and sex. During follow-up, p-PPI users lost significantly more distal tibial total volumetric BMD (ΔTt.BMD: - 8.58 vs. - 2.45 mg/cm, p = 0.012) and cortical volumetric BMD (ΔCt.BMD, - 28.96 vs. -14.07 mg/cm, p = 0.005), and showed a significantly greater loss in tibial bone strength (Δstiffness - 4848.1 vs. 20.7 N/mm, p = 0.029; Δfailure load - 204.5 vs. 16.7 N, p = 0.026) than non-PPI users. At the radius, p-PPI users showed over the 2 years significantly greater increases in cortical porosity and intracortical pore diameter than non-PPI users (ΔCt.Po, p = 0.005; ΔCt.PoDm, p = 0.009). Long-term PPI intake was associated with a significant decline in cortical microarchitecture at the radius and with a significant deterioration of volumetric bone mineral density and strength at the tibia in older patients.

It was widely acknowledged that patients with anorexia nervosa (AN) present a decrease in areal bone mineral density (aBMD), but the effect on bone microarchitecture and other parameters associated with fracture risk have been less well investigated. The two aims of this study were to (i) compare aBMD at various bone sites as determined by DXA, as well as trabecular and cortical volumetric BMD (vBMD) at femoral regions using 3D-Shaper® software, in young women with AN and normal-weight controls (CON) and (ii) determine the factors potentially associated with aBMD and vBMD. Three hundred young women from 18 to 35 years old were enrolled in this study: 209 patients with AN and 91 age-matched normal-weight controls. aBMD was determined with DXA and vBMD by 3D-Shaper® software. Compared with controls, patients with AN presented significantly lower aBMD at all bone sites, but the difference was greater at hip and lumbar spine compared with radius. In whole proximal femur and all femoral compartments, vBMD was also lower in patients, but the difference between groups was greater for cortical vBMD compared with trabecular vBMD. Cortical thickness was also altered but to a lower extent. The bone deterioration induced a decrease in bone structural parameters. In the patients, the independent variables for determining aBMD and vBMD were principally minimal disease-related BMI, menstrual disorder status and duration of amenorrhea. This study confirmed not only that young women with AN present lower aBMD across the skeleton, but it also showed for the first time a concomitant deterioration in trabecular and cortical vBMD and cortical thickness as measured by 3D-Shaper®, leading to a decrease in bone structural parameters. In future, it will be interesting to determine whether 3D-Shaper® parameters are more sensitive than aBMD for monitoring skeletal changes due to weight variations or during therapeutic interventions. It will also be relevant to assess whether these new bone parameters are more predictive of fracture risk than aBMD in these patients.

Hormone replacement therapy in women usually focuses on estrogen and progesterone replacement. But also androgens decrease with age in women. Decrease of estrogen or androgens levels are associated with bone loss, while steroid hormone therapy often leads to negative side effects. A possible solution could be the use of selective receptor modulators (SRMs). Here, a combined treatment with a selective estrogen receptor modulator (raloxifene, RAL) and a selective androgen receptor modulator (ostarine, OST) was investigated in ovariectomized rats. The study was performed using 3-month-old female Sprague-Dawley rats. Fifteen control rats were not ovariectomized (NON-OVX). Sixty rats were ovariectomized and divided into 4 groups (n = 15/group): (1) untreated rats (OVX), (2) rats receiving OST (0.55 ± 0.08 mg/kg body weight [BW]), (3) rats receiving RAL (11.07 ± 1.77 mg/kg BW), (4) rats treated with OST and RAL. The compounds were administered orally as osteoporosis prophylaxis immediately after ovariectomy for up to 13 weeks. Thereafter, the lumbar vertebrae and femora were analyzed.OST + RAL treatment showed a favorable effect on structural and biomechanical bone parameters, demonstrating some advantages over RAL alone. RAL confirmed its antiresorptive effect on bone tissue without causing negative systemic effects. OST alone was less effective in protecting bone tissue. It increased osteoblast number, serum phosphorus, bone magnesium, and inner organ and uterus weight. The adverse effect of OST on bone magnesium level was attenuated when combined with RAL. Conversely, the combined treatment increased serum phosphorus and luteinizing hormone levels, decreased serum magnesium and calcium, and did not attenuate the organ and uterus weight increase observed after OST, raising safety concerns. These findings highlight the need for cautious evaluation of combination therapies and suggest that there is a need for alternative compounds with improved safety profiles for future osteoporosis treatments.