Osteoporosis International最新文献

In a single, large integrated US healthcare system, bisphosphonate treatment initiation for fracture prevention among older adults shifted towards higher-risk populations over a 25-year time period (1998-2022). The temporal trends among women and men who initiated treatment reflected changing practice patterns and both primary and secondary fracture prevention efforts.

Introduction: While bisphosphonate (BP) drugs remain first-line for fracture prevention, treatment has changed over time. This study examines trends over 25 years among adults initiating BP in a single healthcare system.

Methods: Among adults aged 50-89 years who initiated alendronate, risedronate, ibandronate, or zoledronate in Kaiser Permanente Northern California during 1998-2022, age, sex, race and ethnicity, and fracture history were examined. Findings across 5-year periods were evaluated.

Results: A total of 212,289 adults (86.0% women) initiated BP during 1998-2022. After 2008, a much lower proportion of adults who initiated BP were age < 65 years. Across successive 5-year periods, the percentages of women who were age < 65 years were 35.1%, 35.2%, 24.1%, 18.8%, and 17.8%. Among men, these percentages were 26.9%, 25.4%, 17.6%, 12.6%, and 4.7%. In later years, sustained or increasing numbers of adults initiating BP coincided with electronic health record targets for BMD screening (since 2016 for women, 2017-2019 for men), an impact greater for men. The proportions with prior fracture among women initiating BP increased from 21-24% (1998-2007) to 35-38% (2008-2022) after implementing a secondary fracture prevention program for women in 2008. Among men, this proportion increased from 28 to 37%, 40%, and 47% during successive 5-year periods in 1998-2017 (the secondary fracture prevention program for men began in 2015) but fell to 26% in 2018-2022 after BMD screening targeted older men.

Conclusions: In a large primary care population of adults initiating BP, greater treatment of older adults and those with prior fracture highlights the key role of targeted fracture prevention initiatives, sustaining treatment efforts.

Rare genetic variants in genes previously described to be involved in bone monogenic disorders were identified in postmenopausal women split into two groups according to extreme bone mineral density (BMD) values and lumbar spine Z-scores. A pathogenic variant in COL1A2 gene found in a woman with low BMD highlights the overlap between osteogenesis imperfecta and osteoporosis, which may share their genetic etiology. Other variants were not clearly associated with the extreme BMD, suggesting that there is little contribution of rare variants to postmenopausal osteoporosis.

Purpose: We aimed to evaluate whether extreme values of bone mineral density (BMD) in a population-based cohort of postmenopausal women (BARCOS) could be determined by rare genetic variants in genes related to monogenic bone disorders.

Methods: A panel of 127 genes related to different skeletal phenotypes was designed. Massive sequencing by targeted capture of these genes was performed in 104 DNA samples from those women of the BARCOS cohort that exhibited the highest (HZ group) and lowest (LZ group) LS Z-scores, ranging from + 0.70 to + 3.80 and from - 2.35 to - 4.26, respectively. 5'UTR, 3'UTR, splice region, missense, nonsense, and short indel variants with MAF < 0.01 were annotated with CADD version 1.6 and considered in the analysis.

Results: After filtering those variants with CADD > 25 and present only in one of the groups (either LZ or HZ), six variants were detected, most of which (5/6) were in the LZ group in TCIRG1, COL1A2, SEC24D, LRP4, and ANO5 genes, while only one, in the LMNA gene, was in the HZ group. According to the ClinVar database, the COL1A2 variant, causative of a recessive form of osteogenesis imperfecta, is described as pathogenic, while the other variants are considered of uncertain significance (VUS).

Conclusion: The variant identified in COL1A2 in a woman from the LZ group highlights the genetic overlap between monogenic diseases such as osteogenesis imperfecta and complex diseases like osteoporosis. However, the other variants were not clearly associated with the extreme BMD, suggesting that there is little contribution of rare variants to postmenopausal osteoporosis.

Purpose: Osteoporosis has become a global public health concern making prevention and treatment essential to reduce severe consequences for individuals and health systems. This systematic review with meta-analysis aimed to determine the effects of combined protein and exercise interventions compared to (a) exercise alone and (b) protein alone on bone mineral content (BMC) or density (BMD) in middle-aged and older adults.

Methods: We systematically searched Medline, CINAHL, CENTRAL, Web of Science, and SPORTDiscus until 24th January 2023. Pairwise random-effects meta-analyses were performed to calculate weighted mean differences (WMD) with 95% confidence intervals (95% CI). We evaluated risk of bias (Cochrane RoB2) and certainty of evidence (CoE; GRADE). If pooling was not possible, the results were summarized descriptively.

Results: For the comparison of combined protein supplementation and exercise vs. exercise alone, no meta-analysis for BMD (2 RCTs) was possible. For BMC, little to no intervention effect was found (WMD 0.03 kg; 95% CI - 0.00 to 0.05; 4 RCTs; IG = 97/CG = 98; I² = 58.4%). In a sensitivity analysis, restricted to combined milk-protein supplementation and exercise, the result remained similar (0.01 kg; 95% CI - 0.01 to 0.03; 4 RCTs; IG = 71/CG = 71; I² = 0.0%; low CoE). For the comparison of combined protein and exercise interventions vs. protein alone, no RCT on BMC was identified; the results on total or regional BMD (2 RCTs) were inconclusive.

Conclusion: Based on our findings, no robust conclusions can be drawn on whether combining protein and exercise interventions is more beneficial for bone health than one component alone. Sufficiently powered studies with longer duration are required to clarify these questions (CRD42022334026).

In the CNHR study, 35% of postmenopausal women had osteoporosis by BMD or fragility fracture, and 4% had both. Three men ≥ 50 had osteoporosis by BMD or fragility fracture (33.3%; n = 3/9). This suggests that close follow-up of skeletal health is necessary in postmenopausal women, and men ≥ 50 with chronic HypoPT.

Purpose: Chronic hypoparathyroidism (HypoPT) has been associated with decreased bone turnover and abnormalities in bone mineral density (BMD), microarchitecture, and strength. Current guidelines do not recommend systematic evaluation of skeletal health in patients with chronic HypoPT. Our study assessed skeletal health in pre- and postmenopausal women with chronic HypoPT and adult men.

Methods: This prospective study enrolled adults with chronic HypoPT from the Canadian National Hypoparathyroidism Registry. Clinical characteristics, bone fractures, biochemistry, and serum bone biomarkers were assessed at baseline. Skeletal health evaluation included assessments of fragility fractures, BMD at lumbar spine (LS), femoral neck (FN), total hip (TH), 1/3 radial sites, trabecular bone score (TBS), and bone biomarkers.

Results: We present the baseline data of the patients enrolled in the registry. We analyzed a total of 101 patients: 18 men, 35 premenopausal, and 48 postmenopausal women. The mean (SD) age at the onset of HypoPT was 40.7 (16.8) years, and the average disease duration was 11.2 (8.6) years. The most common etiology was postsurgical (74.3% vs. 25.7% non-surgical). Most patients received calcium supplements (89%) and active vitamin D (80%) at baseline. No fragility fractures or low BMD were reported in premenopausal women. However, BMD at LS, FN, TH, and TBS were significantly lower in postmenopausal compared to premenopausal women.

Conclusions: Overall, 35% of postmenopausal women had osteoporosis by BMD or prior fragility fracture, and 4% had both. Three men ≥ 50 years had osteoporosis by BMD or fragility fracture (33.3%; n = 3/9). This study suggests that close follow-up of skeletal health is necessary in postmenopausal women with chronic HypoPT and men ≥ 50 years.

Contrary to popular belief, a recent study did not show increased osteoclastic activity in acute complex regional pain syndrome. Conversely, osteoblastic activity seems to be enhanced. The real meaning of diagnostic tools needs to be reassessed. Therefore, bisphosphonates act through mechanisms of action different from their anti-osteoclastic effect.

Introduction: Bone tissue involvement is a widely acknowledged event in the course of complex regional pain syndrome (CRPS), and it is invariably depicted as "high turnover osteoporosis." This statement needs to be revised in light of a recent biochemical study on bone turnover markers and regulators in patients with early CRPS.

Methods: The real meaning of the findings arising from biochemical, radiological, and histopathological studies and the possible mechanism of action of parenteral bisphosphonates have been reviewed according to the bone metabolism derangement specific to this disease.

Results: Consistent with the results of the recent biochemical study, no reliable data emerge from diagnostic studies sustaining an increased osteoclastic activity. Conversely, osteoblastic activity seems to be enhanced for an increased Wnt signaling due to lower levels of Sclerostin and Dickkopf-1. These results may provide a different and alternative interpretation of previous diagnostic and therapeutic studies.

Conclusions: For the emerging role of bone in CRPS pathogenesis, these remarks could be useful for improving knowledge of the pathophysiology of the disease.

Purpose: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.

Methods: Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined.

Results: Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications.

Conclusion: We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.