GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates

Summary  

This database analysis of over 4,000 German women prescribed oral bisphosphonates between December 2004 and November 2007 showed that compliance and persistence with oral bisphosphonates in German women with osteoporosis were inadequate.     

Sclerostin and DKK1 in postmenopausal osteoporosis treated with denosumab

The bone mass benefits of antiresorbers in postmenopausal osteoporosis are limited by the rapid coupling of decreasing bone resorption with bone formation. Wnt signaling is involved in this coupling process during treatment with bisphosphonates, whereas its role during treatment with the anti‐receptor activator of NF‐κB ligand (RANKL) antibody denosumab is unknown. The study population includes patients participating in a placebo‐controlled trial lasting 36 months: 19 women were on placebo and 24 on subcutaneous 60 mg denosumab every 6 months. All measured parameters (serum C‐terminal telopeptide of type I collagen [sCTX], serum bone alkaline phosphatase [bAP], Dickkopf‐1 [DKK1], and sclerostin) remained unchanged during the observation period in the placebo group. sCTX and bAP were significantly suppressed by denosumab treatment over the entire follow‐up. Denosumab treatment was associated with significant (p < 0.05) increases (28% to 32%) in serum sclerostin over the entire study follow‐up. Serum DKK1 significantly decreased within the first 6 months with a trend for further continuous decreases, which reached statistical significance (p < 0.05) versus placebo group from the 18th month onward. The changes in DKK1 were significantly and positively related with the changes in sCTX and bAP and negatively with hip bone mineral density (BMD) changes. The changes in sclerostin were significantly and negatively related only with those of bAP. The changes in bone turnover markers associated with denosumab treatment of postmenopausal osteoporosis is associated with significant increase in sclerostin similar to those seen after long‐term treatment with bisphosphonates and significant decrease in DKK1. This latter observation might explain the continuous increase over 5 years in BMD observed during treatment of postmenopausal osteoporosis with denosumab. © 2012 American Society for Bone and Mineral Research.     

双膦酸盐类药物治疗骨质疏松症

目的 评价不同类型双膦酸盐药物的临床疗效。方法 骨质疏松妇女360人,随机分成3组,所有患者每天在接受元素钙500 mg和维生素D200IU治疗的同时,分别接受羟乙膦酸钠、阿伦膦酸钠和利塞膦酸钠治疗,其中羟乙膦酸钠200 mg,bid,用2周,间歇11周后再次重复;阿伦膦酸钠10mg,qd;利塞膦酸钠5 mg,qd。3种药物治疗时间均为1年。观察内容包括:骨痛,尿N肽端交联Ⅰ型胶原,NTx和血清骨碱性磷酸酶,BAP,骨密度,不良反应,脊柱新骨折。结果 3组患者经1年治疗,与用药前比较,骨痛症状均有不同程度改善;骨代谢指标N肽端交联Ⅰ型胶原和骨碱性磷酸酶均明显下降(P<0.01);腰椎和髋部骨量均有显著上升(P<0.01):其中阿伦膦酸钠治疗组骨密度腰椎L2-4上升5.51％,股骨颈上升2.66％,股骨粗隆上升4.37％,Ward’s区上升3.13％;利塞膦酸钠治疗组骨密度腰椎L2-4上升4.18％,股骨颈上升2.05％,股骨粗隆上升2.81％,Ward’s区上升3.08％;羟乙膦酸钠治疗组骨密度腰椎L2-4上升3.70％,股骨颈上升1.84％,股骨粗隆上升1.96％,Ward’s区上升1.50％;新骨折发生羟乙膦酸钠组4人,阿伦膦酸钠和利塞膦酸钠组均为1人;各组均未见明显不良反应。 结论双膦酸盐治疗骨质疏松症疗效确切,新型双膦酸盐阿伦膦酸钠和利塞膦酸钠更方便、高效。     

Renal safety in patients treated with bisphosphonates for osteoporosis: A review

Bisphosphonates are widely used for the treatment of osteoporosis and are generally well tolerated. However, the United States Food and Drug Administration safety reports have highlighted the issue of renal safety in bisphosphonate‐treated patients. All bisphosphonates carry labeled “warnings” or a contraindication for use in patients with severe renal impairment (creatinine clearance <30 or <35 mL/min). Data from pivotal trials and their extension studies of bisphosphonates approved for the management of osteoporosis were obtained via PubMed, and were reviewed with support from published articles available on PubMed. Renal safety analyses of pivotal trials of oral alendronate, risedronate, and ibandronate for postmenopausal osteoporosis showed no short‐term or long‐term effects on renal function. Transient postinfusion increases in serum creatinine have been reported in patients receiving intravenous ibandronate and zoledronic acid; however, studies showed that treatment with these agents did not result in long‐term renal function deterioration in clinical trial patients with osteoporosis. All bisphosphonate therapies have “warnings” for use in patients with severe renal impairment. Clinical trial results have shown that even in elderly, frail, osteoporotic patients with renal impairment, intravenous bisphosphonate therapy administration in accordance with the prescribing information did not result in long‐term renal function decline. Physicians should follow guidelines for bisphosphonate therapies administration at all times. © 2013 American Society for Bone and Mineral Research.     

Improvements in hip trabecular,subcortical, and cortical density and mass in postmenopausal women with osteoporosis treated with denosumab

In the FREEDOM study, denosumab treatment (60 mg every 6 months) decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures over 36 months in postmenopausal women with osteoporosis. In a subset of these women, hip quantitative computed tomography (QCT) was performed at baseline and months 12, 24, and 36. These scans were analyzed using Medical Image Analysis Framework (MIAF) software, which allowed assessment of total hip integral, trabecular, subcortical, and cortical compartments; the cortical compartment was further divided into 2 areas of interest (outer and inner cortex). This substudy reports changes in BMD and bone mineral content (BMC) from baseline and compared placebo with denosumab over 36 months of treatment (placebo N = 26; denosumab N = 36). Denosumab treatment resulted in significant improvements in total hip integral volumetric BMD (vBMD) and BMC from baseline at each time point. At month 36, the mean percentage increase from baseline in total hip integral vBMD and BMC was 6.4% and 4.8%, respectively (both p < 0.0001). These gains were accounted for by significant increases in vBMD and BMC in the trabecular, subcortical, and cortical compartments. In the placebo group, total hip integral vBMD and BMC decreased at month 36 from baseline by − 1.5% and − 2.6%, respectively (both p < 0.05). The differences between denosumab and placebo were also significant at months 12, 24, and 36 for integral, trabecular, subcortical, and cortical vBMD and BMC (all p < 0.05 to < 0.0001). While the largest percentage differences occurred in trabecular vBMD and BMC, the largest absolute differences occurred in cortical vBMD and BMC. In summary, denosumab significantly improved both vBMD and BMC from baseline and placebo, assessed by QCT MIAF, in the integral, trabecular, subcortical, and cortical hip compartments, all of which are relevant to bone strength.     

Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis

Summary  

This primary care database survey evaluated whether osteoporotic women treated with bisphosphonates were more adherent to monthly than to weekly treatment. Both compliance (medication possession ratio [MPR]) and persistence (time to discontinuation) were superior in the monthly ibandronate treatment group. Better control of fracture risk may thus be achieved using monthly treatment regimens.     

Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis

Denosumab reduces the risk of new vertebral and nonvertebral fractures. Previous trials suggest that the efficacy of antiresorptives on fractures might differ by patients' characteristics, such as age, bone mineral density (BMD), and fracture history. In the FREEDOM study, 7808 women aged 60 to 90 years with osteoporosis were randomly assigned to receive subcutaneous injections of denosumab (60 mg) or placebo every 6 months for 3 years. New vertebral and nonvertebral fractures were radiologically confirmed. Subgroup analyses described in this article were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups. Compared with placebo, denosumab decreased the risk of new vertebral fractures in the overall study population over 3 years. This effect did not significantly differ for any of the nine subgroups analyzed (p > 0.09 for all potential interactions). Denosumab also reduced all nonvertebral fractures by 20% in the full study cohort over 3 years. This risk reduction was statistically significant in women with a baseline femoral neck BMD T‐score ≤ ?2.5 but not in those with a T‐score > ?2.5; in those with a body mass index (BMI) < 25 kg/m² but not ≥ 25 kg/m²; and in those without but not with a prevalent vertebral fracture. These differential treatment effects were not explained by differences in BMD responses to denosumab. Denosumab 60 mg administered every 6 months for 3 years in women with osteoporosis reduced the risk of new vertebral fractures to a similar degree in all subgroups. The effect of denosumab on nonvertebral fracture risk differed by femoral neck BMD, BMI, and prevalent vertebral fracture at baseline. © 2012 American Society for Bone and Mineral Research     

槲皮素对双膦酸盐治疗老年性骨质疏松患者骨代谢指标改善效果的分析

目的观察槲皮素对双膦酸盐类治疗老年性骨质疏松患者骨代谢指标的影响。方法 216例老年性骨质疏松患者(收治时间:2017年1月至2018年1月)以信封随机分组法分为常规对照组(共108例,双膦酸盐+骨健康补充剂治疗6个月)和槲皮补充组(共108例,以双膦酸盐+骨健康补充剂+槲皮素治疗6个月)。分析常规对照组和槲皮补充组的主客观疗效(总有效率、ODI评分、SF-36评分及VAS视觉评分)、骨密度及骨代谢指标(CTX-1、BALP、BGP、t PINP、PTH)的差异。结果与治疗前比较,槲皮补充组和常规对照组治疗后的前臂远端骨密度、BALP及SF-36评分均提升,而VAS评分、ODI评分、PTH、BGP、CTX-1、t PINP均下降(P均0.05),但槲皮补充组前臂远端骨密度、BALP及SF-36评分的升幅更大,VAS评分、ODI评分、PTH、BGP、CTX-1、t PINP的降幅更大。槲皮补充组临床总有效率(87.04%)显著优于常规对照组(68.52%)(P0.05)。结论补充槲皮素辅助双膦酸盐治疗老年性骨质疏松患者,可显著改善患者骨密度指标、疼痛症状、功能障碍情况及骨代谢指标的异常表达,提升患者生活质量。     

长期应用双膦酸盐类药物对老年性骨质疏松骨折愈合过程的影响

目的探讨长期应用双膦酸盐类药物(阿仑膦酸钠)治疗老年性骨质疏松症所引起的骨质疏松骨折的可行性以及长期应用双膦酸盐类药物在骨质疏松骨折愈合过程中对于骨组织的影响,为临床正确应用抗骨吸收药物治疗原发性骨质疏松症提供科学理论根据。方法选择90只12月龄雌性SD大鼠,常规饲养至15月龄左右。每组于骨折造模前2周以及骨折造模后并开始给药后的2周、4周、8周、12周5个时间点,进行X线、组织形态、骨代谢生化标志物以及micro-CT的检测。结果 X线:实验组A早期有明显的梭形外骨痂,但12周未愈合。组织形态学:实验组A早期见大量软骨细胞,愈合晚期虽有改建后成熟骨小梁和新生血管,但骨折处未愈合。骨代谢生化标志物:BAP:实验组A于12周的成骨活性均低于实验组B和实验组C;CTX-1:实验组A于8周后其水平逐渐增高。Micro-CT:实验组A的骨小梁厚度、骨小梁数量减少;骨小梁分离度增加。(统计数据均利用SPSS16.0进行统计分析,P<0.05)。结论长期应用双膦酸盐药物治疗老年性骨质疏松引起的骨折会导致骨折断端愈合延迟甚至不愈合。     

Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fracture rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a "virtual untreated twin" cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw. Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile.     

绝经后女性类风湿关节炎患者骨质疏松影响因素的回顾性研究

目的 通过分析绝经后女性类风湿性关节炎(RA)患者骨密度与临床资料的相关性,探讨影响骨密度的相关因素。方法 收集64例绝经后女性RA患者一般临床资料、腰椎及股骨的平均骨密度（BMD)、骨代谢指标、实验室检查指标,根据骨密度分为骨质疏松组和非骨质疏松组,比较临床资料并分析可能影响骨密度的因素。结果 64例患者平均年龄(58. 47 ±5.81) 岁,平均病程5.5(2.0,12.0)年。骨质疏松比例为62.5% (40/64)。骨质疏松组的绝经时间、ESR、纤维蛋白原、DAS28高于非骨质疏松组,绝经年龄、体重、BMI、ALB、DMARDs及抗骨吸收药物使用率低于非骨质疏松组,病程2年以上的患者骨质疏松发病率较高,其炎症指标亦高于同病程非骨质疏松组。简单相关分析提示BMD与绝经年龄、体重、BMI、ALB正相关,与 DAS28负相关。Logistic回归分析提示绝经年龄（OR = 4. 750,95%CI：1. 30247. 327,P = 0. 018)是影响绝经后女性RA患者 BMD的独立因素。多重线性回归方程提示BMD与BMI正相关,与DAS28负相关。结论 绝经后RA患者BMD受绝经年龄、BMI、DAS28的影响。绝经年龄是影响绝经后女性RA患者BMD的独立因素。     

Gender differences in osteoporosis screening: retrospective analysis

Introduction

Osteoporosis is a common disease affecting 20?% of all men. It accounts for more than 1.5 million fractures yearly in the USA. Up to 20?% of patients who sustain hip fractures die within the first 12?months from related complications. The Endocrine Society recommends screening all men 70?years or older regardless of risk factors. There are little data comparing gender-specific osteoporosis screening rates. The aim of the study is to identify any gender difference in osteoporosis screening.

Methods

We conducted a retrospective study to determine the screening rates for osteoporosis in males and females in our Division of Internal Medicine, university-based outpatient clinic (UBC). Males aged 70?C75?years and females aged 65?C70?years with a primary care physician (PCP) at our UBC, who have had at least one routine health maintenance exam (HME) since 2002, were included.

Results

A total of 8,262 patients who met the age criteria were identified: 3,255 (39.4?%) males and 5,007 (60.6?%) females. Of the 3,255 male patients, 342 patients had their PCP at our UBC and had at least one HME; of those, 63 patients had DXA performed for an osteoporosis screening rate of 18.4?%. Of the 5,007 female patients, 668 patients had their PCP at our UBC and had at least one HME; of those, 402 patients had DXA performed for an osteoporosis screening rate of 60?%.

Conclusion

Males are screened less frequently although they have a comparable prevalence of osteoporosis.     

Effects of teriparatide on serum calcium in postmenopausal women with osteoporosis previously treated with raloxifene or alendronate

SUMMARY: The effect of teriparatide (20 microg/day) on serum calcium was examined in postmenopausal women previously treated with alendronate or raloxifene. Women previously treated with alendronate or raloxifene who added teriparatide or switched to teriparatide did not have clinically meaningful increases in mean predose serum calcium. INTRODUCTION: The effects of a 6-month treatment with teriparatide (20 microg/day; rhPTH(1-34), TPTD) on serum calcium (Ca) was examined in a prospective study of postmenopausal women previously treated with alendronate (70 mg/week or 10 mg/day [ALN] or raloxifene 60 mg/d [RLX]) for > or =18 months. METHODS: Women continued their usual ALN or RLX during a 2-month antiresorptive phase. Women previously treated with ALN were randomized to add TPTD (n = 52) or switch to TPTD (n = 50) and women previously treated with RLX were randomized to add TPTD (n = 47) or switch to TPTD (n = 49). All were to take at least 500 mg/day of elemental Ca and 400-800 IU/day of vitamin D. RESULTS: Predose mean serum Ca did not significantly change in groups adding TPTD to either RLX or ALN treatment. In patients who switched from RLX or ALN to TPTD, mean serum Ca increased by 0.05 mmol/L and 0.04 mmol/L respectively. Only 1 patient had the predefined calcium endpoint of serum calcium > 2.76 mmol/L (11 mg/dL) at more than one visit. CONCLUSIONS: Women previously treated with ALN or RLX who added TPTD or switched to TPTD did not have clinically meaningful increases in mean predose serum Ca.