Calcified Tissue International最新文献

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.

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.

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.

Introduction: 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.

Methods: We summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history.

Results: We recruited 350 adults with a clinical diagnosis of OI in 27 European referral centres between June 2017 and October 2022. Overall, 266 (76.2%) had type I OI, 55 (15.8%) had type IV, and 19 (5.4%) had type III. The type was unknown in 9 (2.6%). Blue sclera were noted in 80.8%, and 35.8% had dentinogenesis imperfecta. Bisphosphonates had been administered to 28.1% in the 2 years prior to enrolment. Pathogenic variants in COL1A1 or COL1A2 were found in 87.6%. Fractures occurring in the 2 years prior to enrolment were not associated with bone density.

Conclusions: The TOPaZ population represents a unique cohort with which to study the genetic epidemiology and outcome of OI in relation to bone density and biochemical markers of bone turnover. When the trial reports, it will also provide new insights into the effect of an anabolic therapy, followed by antiresorptive treatment in the management of OI.

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.

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.

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.

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.

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/cm³, p = 0.012) and cortical volumetric BMD (ΔCt.BMD, - 28.96 vs. -14.07 mg/cm³, 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.

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

Methods: Data from 3,174 participants aged 20-54 years from the 3rd (2006-2008) and 4th (2017-2019) HUNT Study surveys were linked to the Medical Birth Registry of Norway. BMD and BMC of femoral neck were measured using dual-energy X-ray absorptiometry (DXA). Linear regression estimated mean differences in BMD and BMC by birth characteristics, adjusting for sex, birth year, age at scan, maternal age, and maternal morbidity.

Results:  At bone densitometry, participants had a mean age of 34.2 years, with mean BMD of 0.971 g/cm², and mean BMC of 5.398 g, at the femoral neck. A standard deviation (SD) increase in ponderal index (PI) and birth weight was associated with higher BMD of 0.024 g/cm² (95% CI 0.006, 0.042) and 0.015 g/cm² (95% CI 0.009, 0.022). Individuals born large for gestational age (LGA) had 0.023 g/cm² (95% CI 0.007, 0.039) higher BMD than those born appropriate for gestational age (AGA), while low birth weight (LBW)(< 2.5 kg) was associated with - 0.028 g/cm² (95% CI - 0.053, - 0.003) lower BMD. For BMC, an SD increase in PI and birth weight was associated with 0.171 g (95% CI 0.048, 0.293) and 0.146 g (95% CI 0.112, 0.181) higher BMC, respectively. LGA had 0.206 g (95% CI 0.090, 0.313) higher BMC, while LBW was associated with - 0.298 g (95% CI - 0.469, - 0.127) lower BMC.

Conclusion: Higher ponderal index, birth weight, and gestational age were positively associated with BMD and BMC in young adulthood.