Physical function and lean body mass as predictors of bone loss after hip fracture: a prospective follow-up study
- 作者列表："Tuuli H. Suominen","Johanna Edgren","Anu Salpakoski","Mauri Kallinen","Tomas Cervinka","Timo Rantalainen","Timo Törmäkangas","Ari Heinonen","Sarianna Sipilä
Abstract Background Predictors of bone deterioration after hip fracture have not been well characterized. The aim of this study was to examine the associations of physical function and lean body mass (LBM) with loss of bone density and strength in older people recovering from a hip fracture. Methods A total of 81 over 60-year-old, community-dwelling men and women operated for a hip fracture participated in this 1-year prospective follow-up study. Distal tibia total volumetric bone mineral density (vBMDTOT, mg/cm3) and compressive strength index (BSI, g2/cm4) and mid-tibia cortical vBMD (vBMDCO, mg/cm3) and bending strength index (SSI, mm3) were assessed in both legs by peripheral quantitative computed tomography (pQCT) at baseline (on average 10 weeks after fracture) and at 12 months. At baseline, LBM was measured with a bioimpedance device and physical function with the Short Physical Performance Battery (SPPB) and perceived difficulty in walking outdoors. Robust multivariable linear regression models were used to estimate the associations of physical function and LBM with the change in bone parameters at 12-months. Results The mean change in distal tibia vBMDTOT and BSI in both legs ranged from − 0.9 to − 2.5%. The change in mid-tibia vBMDCO and SSI ranged from − 0.5 to − 2.1%. A lower SPPB score, difficulty in walking outdoors and lower LBM predicted greater decline in distal tibia vBMDTOT in both legs. A lower SPPB score and difficulty in walking outdoors were also associated with a greater decline in distal tibia BSI in both legs. At the midshaft site, a lower SPPB score and lower LBM were associated with greater decline in SSI on the fractured side. Conclusions Older hip fracture patients with low physical function and lower LBM may be at risk for greater decline in tibia bone properties during the first post-fracture year. Acknowledgement of the risk factors could assist in developing interventions and care to promote bone health and overall recovery. Trial registration ISRCTN, ISRCTN53680197 . The trial was registered retrospectively but before the recruitment was completed. Registered March 3, 2010.
摘要背景: 髋部骨折后骨恶化的预测因素尚未得到很好的描述。本研究的目的是检查髋部骨折恢复期老年人的身体功能和瘦体重 (LBM) 与骨密度和力量丧失的相关性。方法共有 81 名 60 岁以上的社区居民参与了这项为期 1 年的前瞻性随访研究。胫骨远端总体积骨密度 (vBMDTOT，mg/cm3) 和抗压强度指数 (BSI，g2/cm4) 和胫骨中段皮质 vBMD (vBMDCO，mg/cm3) 基线时通过外周定量计算机断层扫描 (pQCT) 评估双腿的弯曲强度指数 (SSI，mm3)(骨折后平均 10-周) 和 12-月。基线时，用生物阻抗装置测量 LBM，用短物理性能电池 (SPPB) 和自觉户外行走困难测量身体功能。使用稳健的多变量线性回归模型估计 12 个月时身体功能和 LBM 与骨参数变化的相关性。结果两腿胫骨远端 vBMDTOT 和 BSI 的平均变化范围为-0.9 至-2.5%。胫骨中段 vBMDCO 和 SSI 的变化范围为-0.5 至-2.1%。较低的 SPPB 评分、户外行走困难和较低的 LBM 预测双腿胫骨远端 vBMDTOT 下降幅度更大。较低的 SPPB 评分和户外行走困难也与两腿胫骨远端 BSI 下降幅度较大相关。在中轴部位，较低的 SPPB 评分和较低的 LBM 与骨折侧 SSI 的更大下降相关。结论在骨折后第一年，身体功能低下和 LBM 较低的老年髋部骨折患者可能有胫骨骨性能下降的风险。对风险因素的承认有助于制定干预措施和护理，以促进骨骼健康和整体恢复。试验注册 ISRCTN，ISRCTN53680197。试验是回顾性登记的，但在招募完成之前。2010 年 3 月 3 日注册。
METHODS::A major challenge in translating findings from genome-wide association studies (GWAS) to biological mechanisms is pinpointing functional variants because only a very small percentage of variants associated with a given trait actually impact the trait. We used an extensive epigenetics, transcriptomics, and genetics analysis of the TBX15/WARS2 neighbourhood to prioritize this region's best-candidate causal variants for the genetic risk of osteoporosis (estimated bone density, eBMD) and obesity (waist-hip ratio or waist circumference adjusted for body mass index). TBX15 encodes a transcription factor that is important in bone development and adipose biology. Manual curation of 692 GWAS-derived variants gave eight strong candidates for causal SNPs that modulate TBX15 transcription in subcutaneous adipose tissue (SAT) or osteoblasts, which highly and specifically express this gene. None of these SNPs were prioritized by Bayesian fine-mapping. The eight regulatory causal SNPs were in enhancer or promoter chromatin seen preferentially in SAT or osteoblasts at TBX15 intron-1 or upstream. They overlap strongly predicted, allele-specific transcription factor binding sites. Our analysis suggests that these SNPs act independently of two missense SNPs in TBX15. Remarkably, five of the regulatory SNPs were associated with eBMD and obesity and had the same trait-increasing allele for both. We found that WARS2 obesity-related SNPs can be ascribed to high linkage disequilibrium with TBX15 intron-1 SNPs. Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk.
METHODS:PURPOSE:Systemic mastocytosis (SM) is characterized by the expansion of clonal mast cells that infiltrate various organ systems. The extent of organ infiltration and subsequent organ damage distinguishes between indolent SM (ISM) defined by a nearly normal life expectancy and advanced SM (AdvSM) defined by poor prognosis. In ISM, measurement of the bone mineral density (BMD) frequently reveals osteoporosis. In contrast, the clinical implication of an increased BMD and osteosclerosis remains unclear. METHODS:BMD was evaluated in 61 patients with mastocytosis (ISM, n = 29, 48%; AdvSM, n = 32, 52%). We correlated the prevalence of osteoporosis, increased BMD and osteosclerosis with clinical parameters, disease variant and prognosis. RESULTS:Osteoporosis was detected in 11/29 (38%) patients with ISM but only in 2/32 (6%) patients with AdvSM (p = 0.004). An increased BMD was detected in 1/29 (3%) patients with ISM and 24/32 (75%) patients with AdvSM (p < 0.001) while osteosclerosis was only detected in AdvSM patients (16/32, 50%). AdvSM patients with increased BMD had higher levels of bone marrow mast cell infiltration, higher serum tryptase and alkaline phosphatase levels compared to ISM as well as higher number of high-molecular risk mutations (p < 0.05). In addition, we found that the prognosis of AdvSM patients with increased BMD is inferior compared to those without increased BMD (median overall survival 3.6 years versus not reached, p = 0.031). CONCLUSIONS:Osteoporosis is a common feature in ISM but not in AdvSM. An increased BMD is frequently present in AdvSM but not in ISM and is associated with more advanced disease and inferior outcome.
METHODS::We present salmon calcitonin (SCT) loaded Hydroxyapatite nanoparticles (HAP-NPs) for sublingual osteoporosis therapy. Surface stabilized HAP-NPs were prepared by aqueous precipitation. SCT was loaded by ionic complexation, as confirmed by FTIR. SCT-HAP-NPs exhibited high loading efficiency (~85%), average size (~100nm), and zeta potential (~-25 mv). Stability of SCT was established by circular dichroism spectroscopy and HPLC analysis. Confocal laser scanning microscopy confirmed deep penetration of SCT-HAP-NPs into the mucosa with >4-fold enhancement in permeability relative to SCT solution. Sublingual SCT-HAP-NPs revealed relative bioavailability of ~15% compared to the subcutaneous injection in rabbits (200iu). Significant and comparable improvement in serum biomarkers with increase in bone mass and mechanical strength and decreased bone erosion compared to subcutaneous SCT was confirmed in ovariectomized (OVX) osteoporosis rat model. Such comparable pharmacodynamic effect at the same dose suggested targeted bone delivery and promise of sublingual SCT-HAP-NPs as a non-invasive alternative to the injection.