Daily nasal spray of hPTH(1–34) for 3 months increases bone mass in osteoporotic subjects: a pilot study

Introduction Although intermittent parathyroid hormone (PTH) injection can lead to strong anabolic effects on bone, daily subcutaneous injection is a disadvantage for patient acceptance. We have developed a nasal spray formula of parathyroid peptide [hPTH(1–34)] with peak serum hPTH(1–34) concentrations by nasal spray of 1,000 μg similar to those by subcutaneous injections of 20 μg hPTH(1–34).Methods To determine the clinical efficacy and safety of nasal hPTH(1–34) spray, a randomized, open-labeled clinical trial was conducted in subjects with osteoporosis. Ninety osteoporotic subjects age 52–84 years (mean 66.5 years) were randomly assigned to receive either 250 μg (PTH250, n=31), 500 μg (PTH500, n=30), or 1,000 μg (PTH1000, n=29) of daily nasal hPTH(1–34) spray for 3 months. All received daily supplements of 300 mg calcium and 200 IU vitamin D₃.Results Daily nasal hPTH(1–34) spray for 3 months increased lumbar bone mineral density (L-BMD) in a dose-dependent manner, and the PTH1000 group showed a 2.4% increase in L-BMD from baseline. Only the 1,000-μg dose produced consistent and statistically significant changes in markers of bone turnover; after 3 months, median serum type I procollagen N-propeptide (PINP) and osteocalcin increased 14.8% and 19.4% from baseline, while urinary type I collagen N-telopeptide (NTX) decreased 16.4%. Seven subjects developed transient hypercalcemia at 3 h after nasal hPTH(1–34) spray, but none of the subjects developed sustained hypercalcemia.Conclusion These observations demonstrate that nasal hPTH(1–34) spray is safe and well tolerated and can rapidly increase L-BMD. The results warrant further studies to examine its long-term efficacy on bone mass and fractures.     

Effects of physical activity and dietary calcium intake on bone mineral density and osteoporosis risk in a rural Thai population

The objective of the study was to determine the effects of modifiable risk factors on bone mineral density in postmenopausal Thai women. Dietary calcium intake (g/day), energy expenditure (kcal/day), and sunlight exposure (h/day) were assessed in 129 rural Thai women aged 63 years (range 50 to 84 years). Bone mineral density (BMD) at the femoral neck, lumbar spine, and distal radius were measured by dual-energy X-ray absorptiometry (DXA). The average dietary calcium intake was 236 ± 188 g/day (mean ± SD), while the energy expenditure was 2,118 ± 656 kcal/day with 1.1 ± 1.7 h of sunlight exposure. In multiple linear regression analysis, dietary calcium intake, energy expenditure, and years since menopause were significant and independent predictors of BMD at various sites. The three factors together accounted for between 35% and 45% of the variance of BMD. The prevalence of osteoporosis (defined as BMD T-scores –2.5) was 33% at the femoral neck, 42% at the lumbar spine, and 35% at the distal radius. The risk of osteoporosis was higher in women with lower dietary calcium intake (138 mg/day; prevalence rate ratio [PRR], 1.4; 95% confidence interval [CI], 1.0 to 1.9), lower energy expenditure (1,682 kcal; PRR, 1.7; 95% CI, 1.2 to 2.3), and greater years since menopause (6 years; PRR, 2.6; 95% CI, 1.2 to 5.8). The population attributable risk fraction of osteoporosis risk due to the three factors was 70%. These results suggest that in the Thai population, low dietary calcium intake and low physical activity together with advancing years since menopause were independent risk factors for low BMD.     

沈阳128例男性肥胖和骨密度的关系

目的 研究肥胖与骨密度(BMD)之间的关系,探讨不同的肥胖程度对我国沈阳地区中老年人群骨密度的影响,同时研究代谢综合征(MS)与骨密度之间的关系.方法 收集来我院的128例体检男性,运用双能X线骨密度仪测量受检者的骨密度,根据腰臀比(WHR)和腰围(WC)分别分组,比较不同肥胖程度患者的骨密度情况,分析腰臀比、腰围两者与骨密度的关系.结果 根据腰臀比分组,中老年男性各组骨密度没有差异;根据腰围分组,仅有WC>100 cm的受检者,其L_1的BMD明显高于WC<90 cm时的BMD.多元逐步回归分析示除L_3的BMD外,各项骨密度与腰围呈正相关;左右股骨颈及左全身的BMD与年龄呈负相关;仅左股骨颈和L_(2-4)的骨密度与腰臀比呈负相关.3个代谢综合征成分组和代谢综合征组,L_1的BMD高于无代谢综合征成分的BMD.结论 腰围可能是评价中心型肥胖和骨密度之间关系的较佳指标.适当治疗代谢综合征患者的肥胖,可避免骨量的丢失,预防骨质疏松症.     

Ex vivo characterization of articular cartilage and bone lesions in a rabbit ACL transection model of osteoarthritis using MRI and micro-CT

OBJECTIVE: To characterize the rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) at various stages of disease using high-resolution 3-D medical imaging systems, which, in turn, will facilitate future longitudinal studies evaluating disease progression and response to therapy in live animals. METHODS: Degenerative changes in femorotibial cartilage, volumetric bone mineral density (vBMD), bone volume fraction (BV/TV), and osteophyte volume were characterized ex vivo using 4-T magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) at 4, 8, and 12 weeks post-ACLT. These changes were subsequently correlated to macroscopic joint evaluation. RESULTS: Macroscopic assessment demonstrated progressive cartilage degeneration post-surgery, which was significantly correlated to MRI evaluation (r=0.82, P<0.0001). Linear regression analysis indicated that vBMD and BV/TV are linearly related such that as vBMD increases, BV/TV increases (P<0.0001). Micro-CT revealed bone loss at 4 and 8 weeks post-ACLT, but recovery to control values at 12 weeks post-ACLT. Volumetric BMD was not strongly correlated with macroscopic assessment of articular cartilage degeneration (r=-0.35, P<0.0001). Quantitative measurement of osteophyte volume demonstrated a statistically significant difference (with respect to control groups) at both 8 and 12 weeks post-ACLT, but not at 4 weeks post-ACLT. CONCLUSIONS: The rabbit ACLT model of OA demonstrates progressive cartilage degeneration and intermediate bone changes at 4, 8, and 12 weeks post-surgery. Cartilage and bone lesions were characterized ex vivo using 4-T MRI and micro-CT, and MRI assessment of cartilage degeneration was correlated to macroscopic grading.     

新疆乌鲁木齐市某社区维吾尔族女性跟骨骨密度与代谢综合征相关性分析

目的探索代谢综合征(MS)与不同年龄及代谢状态下维吾尔族女性定量骨超声检测跟骨骨密度(T值)与其之间的相关性。方法横断面研究,对象为新疆乌鲁木齐市二道桥某社区常住维族女性。按年龄分组,观察不同年龄段维族女性骨量的变化。按中华医学会糖尿病分会(CDS)[1]诊断MS的诊断标准,将549名女性分为高血压组136例,血压正常组413例;糖尿病组103例,血糖正常组446例;单纯肥胖或超重组290例,体重正常组259例;血脂紊乱组157例,血脂正常组392例;MS组86例,非MS组463例。根据既往史是否绝经分为未绝经组339例,绝经组182例;并用线性回归分析,研究跟骨骨密度的独立影响因素。结果高血压、糖代谢异常、MS组骨量T值均低于其代谢正常组,差异有统计学意义(均P0.05);高血压、糖代谢异常、超重或肥胖、MS组骨量减少、骨质疏松的患病率均高于其代谢正常组,差异有统计学意义(均P0.05);按年龄分组,不同组间T值不完全相同,随年龄增长,骨量减少的患病率升高,差异有统计学意义(P0.05);按是否合并绝经分组,绝经组骨量减少、骨质疏松的患病率明显升高,差异有统计学意义(P0.05)。结论 MS作为多种代谢异常的症候群,骨量减少的患病率高,是骨质疏松发生的高风险人群。绝经是女性骨量减少的独立危险因素。     

东亚人群LRPS基因A1330V位点多态性与骨密度相关性的M eta分析

目的 利用Meta分析的方法,综合评价LRPS基因A1330V位点多态性与东亚人群骨密度(BMD )的相关性。方法 计算机检索Pubmed , Embase、中国生物医学文献数据库和万方数据库数据库等,并手工检索相关杂志,收集有关东亚人群LRPS基因A1330V位点多态性的基因型频率与BMD相关性的研究。检索时间截止至2012年11月。在评价纳人研究质量,提取有效数据后,采用Stata 12.0软件进行Meta分析。结果 共11项研究符合既定的纳人和排除标准,合计5906名研究对象。Meta分析结果显示:AA基因型较AV/VV基因型腰椎BMD高,且差异有统计学意义[SMD =0.107, 95% CI (0.044,0. 171)。在股骨颈BMD方面,AA基因型高于AV/VV基因型[ SMD =0. 190, 95% CI (0. 034, 0. 346) ]。 AA基因型的挠骨、全身BMD也高于AV/VV基因型。但是,AA基因型群体的转子间BMD与AV/VV基因型的差异无统计学意义[SMD =0. 090, 95% CI(-0.029, 1. 143)]。除腰椎、转子间BMD以外,AA基因型群体的股骨颈、挠骨以及全身BMD高于VV基因型,但此基因型间比较的纳人研究数量过少,证据尚不充分。结论 本Meta分析结果提示,东亚人群中LRPS基因A1330V位点的突变可能与骨密度的变化具有相关性,尤其AA基因型人群在股骨颈、腰椎部位有比AV/VV或VV基因型人群更高的骨密度值。但目前的结论尚需进一步大样本、高质量的研究去验证。