Osteoclasts derived from patients with neurofibromatosis 1 (NF1) display insensitivity to bisphosphonates in vitro

A total of 20 patients with neurofibromatosis 1 (NF1) were screened for NF1-related osteoporosis, and blood samples were collected for isolation of peripheral blood osteoclast progenitors. Patients with NF1 had higher levels of serum bone turnover markers (CTX and PINP) compared to controls. In addition, persons with high bone resorption in vitro on average had high levels of serum CTX. Of the 20 patients with NF1, 15 had low bone mineral density (osteopenia/osteoporosis), but these 15 patients did not have marked risk factors for low bone mineral density. Thus, we recommend screening for osteoporosis to all adult patients with NF1. Our aim was also to characterize the effects of bisphosphonates on NF1 osteoclasts in vitro. NF1 osteoclasts and osteoclasts from healthy controls in vitro were treated with zoledronic acid, alendronate and clodronate. These bisphosphonates caused a marked reduction in the number of normal control osteoclasts in vitro, while only a slight change was observed in the number of NF1 osteoclasts. Ras-inhibitor FTS counteracted this NF1-related insensitivity to zoledronic acid, suggesting that Ras may play a role in this phenomenon.     

Neurofibromatosis 1-Related Osteopenia Often Progresses to Osteoporosis in 12 Years

The current study is based on our earlier investigation carried out in 1999, where bone mineral density (BMD) of 35 neurofibromatosis type 1 (NF1) patients was measured and osteoporosis was shown to be common in NF1. The findings have been confirmed by a number of later publications. The purpose of the current longitudinal study was to assess the bone health of these 35 NF1 patients 12 years after the initial study. A total of 28 patients were reached, and BMD of 19 patients was subsequently remeasured. Fracture history of 28/35 NF1 patients who were reached was verified from the medical records. Six NF1 patients had osteoporosis in 1999, and three of them had an osteoporotic fracture between 1999 and 2011, showing an increased fracture risk compared to NF1 patients without osteoporosis. BMD of 19 patients was remeasured in 2011, and four patients who had osteopenia in 1999 had osteoporosis in 2011. The decrease in BMD was not explained by changes in smoking habits, physical activity, sunlight exposure, body mass index, or laboratory parameters, even though secondary hyperparathyroidism was common. Osteoporosis was found in 2011 in patients aged 37 years or older, both men and women. The results showed that NF1-related osteopenia often progresses to osteoporosis since BMD decreases with aging even in young patients. Even though our sample size was 19 patients, we recommend follow-up of NF1 patients with osteopenia and consideration of prophylactic measures to prevent osteoporosis and associated fracture risk.     

Persistence with osteoporosis medication among newly-treated osteoporotic patients

Low persistence with osteoporosis medication is associated with higher fracture risk. Previous studies estimated that 1-year persistence with osteoporosis medication is low. Our aim was to study persistence with osteoporosis medication among patients with long-term follow-up (to 5 years). The InterAction Database (IADB) was used to analyze persistence of 8610 Dutch patients initiating osteoporosis drugs between 2003 and 2011. Drugs under study were alendronate, risedronate, ibandronate, etidronate, raloxifene and strontium ranelate. Cumulative persistence rates were calculated after different time frames (3 months–5 years) using survival analysis. Multivariate Cox proportional hazard analyses were used to identify determinants of non-persistence. Furthermore, switching rates of persistent patients who initiated bisphosphonate therapy were analyzed. Persistence with osteoporosis therapy was 70.7 % (95 % CI, 69.7–71.7), 58.5 % (95 % CI, 57.4–59.6 %), 25.3 % (95 % CI, 24.1–26.5) after 6 months, 1 and 5 years, respectively. Determinants associated with higher risk to non-persistence within the first year were daily dosing regimen [HR, 1.76 (95 % CI, 1.46–2.14)], age <60 years [HR, 1.26 (95 % CI, 1.19–1.34)] and use of glucocorticoids [HR, 1.16 (95 % CI, 1.07–1.26)]. Monthly dosing schedule and use of generic brands of alendronate did not show a significant association with non-persistence. Approximately 4.0 % of patients initiating therapy with weekly alendronate or weekly risedronate switched therapy. Persistence with osteoporosis medication is low. Because low persistence is strongly associated with higher fracture risk, interventions to improve persistence are recommended. This study identified several patient groups in whom such interventions may be most relevant.     

Adherence with bisphosphonate therapy and change in bone mineral density among women with osteoporosis or osteopenia in clinical practice

Summary

In clinical practice, adherence with bisphosphonate therapy varies greatly among women with osteoporosis or osteopenia. Our study suggests that better adherence with bisphosphonates confers tangible benefits in terms of graded increases in bone mineral density. Interventions to improve drug adherence should be an important component of disease management.

Introduction

In clinical trials, bisphosphonates have been found to increase bone mineral density (BMD) in women with osteoporosis or osteopenia. In clinical practice, where drug adherence is more variable, change in BMD with bisphosphonate therapy—overall and by level of adherence—is largely unknown.

Methods

A retrospective cohort study was conducted at Henry Ford Health System (Detroit, MI, USA). Study subjects were women who had low BMD at the left total hip (T-score?<??1.0), began oral bisphosphonate therapy, and had ≥1 BMD measurements at the left total hip ≥6 months following treatment initiation. Change in BMD was calculated between the most recent pretreatment scan and the first follow-up scan. Adherence (i.e., medication possession ratio (MPR)) was measured from therapy initiation to the first follow-up scan.

Results

Among 644 subjects, mean age was 66 years, pretreatment BMD was 0.73 g/cm², and pretreatment T-score was ?1.8. Over a mean follow-up of 27.1 months, mean MPR was 0.57 (95 % CI, 0.54 and 0.59), and mean percentage change in BMD was 1.5 % (1.1 and 1.9 %). Within the MPR strata (five consecutive equi-intervals, from low (0–0.19) to high (0.80–1.0)), mean change in BMD was ?0.8 % (?1.6 and 0.1 %), 0.7 % (?0.3 and 1.7 %), 2.1 % (1.1 and 3.0 %), 2.1 % (1.4 and 2.9 %), and 2.9 % (2.3 and 3.5 %), respectively. In adjusted analyses, percentage change in BMD was higher (by 1.4–3.4 %, p?<?0.05 for all) in the highest four MPR intervals, respectively, versus MPR 0–0.19.

Conclusions

Among women with osteoporosis or osteopenia in clinical practice, better adherence with bisphosphonates appears to confer tangible benefits in terms of increases in BMD.     

Changes in bone mineral density (BMD): a longitudinal study of osteoporosis patients in the real-world setting

Summary

In clinical practice, the frequency of patients achieving improved T-scores and the expected change in bone mineral density (BMD) according to osteoporosis drugs is unknown. We found that osteoporosis medications infrequently achieve improved femoral neck T-scores over 1.2 years. BMD increases were more often seen with IV bisphosphonates and denosumab.

Purpose

To determine the frequency of osteoporosis patients achieving improvement in T-scores and quantify the change in bone mineral density (BMD) over time according to osteoporosis medication use.

Methods

The study included all patients receiving clinical care at United Osteoporosis Centers, Gainesville, GA, 1995–2015, who had at least two measures of femoral neck BMD (N?=?1232). We evaluated successive pairs of BMD tests to describe the distribution of transitions between T-score categories. Generalized estimating equations were used to estimate %BMD change between successive pairs of BMD tests according to osteoporosis medication, adjusted for age, sex, height, weight, baseline BMD, previous fracture, and follow-up time.

Results

Mean (±SD) age was 68 (±10) years, and 90% of patients were women. Mean baseline T-score was ??2.04 (±?0.85). In total, 1232 patients had 4918 pairs of successive BMD tests, with a mean 1.2 years (±?0.9) between assessments. Frequency of transition to an improved T-score category was 41% when prior T-score ≤???3.5, and 15% when prior T-score ??1.99 to ??1.50. Most individuals (69%) remained in the same T-score category. BMD increased 0.54% (95% CI 0.23–0.85%) with IV bisphosphonates and 1.23% (95% CI 0.56–1.90%) with denosumab, whereas no significant change was seen with oral bisphosphonates, teriparatide, or raloxifene.

Conclusions

Osteoporosis patients are unlikely to improve femoral neck T-scores over 1.2 years. Additional studies are needed to determine the optimal time to repeat BMD testing while receiving osteoporosis treatment and to determine whether fracture risk is reduced in patients who achieve target T-scores.

     

Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study.

Bone loss is a common complication in patients before and after liver transplantation (LT). The aim of this study was to investigate the efficacy of prophylactic treatment with bisphosphonates after LT in preventing progressive bone loss in LT patients. We included 136 patients with end-stage liver diseases awaiting LT. Bone mineral density (BMD) (by dual X-ray absorptiometry) and markers of bone metabolism were determined before, and 4, 12, 24, 36, and 48 months after LT. All patients received vitamin D and calcium supplementation before and after LT, those with osteopenia or osteoporosis prior to LT were additionally treated with alendronate following LT. Decreased BMD was seen in a high percentage of patients undergoing LT (osteopenia 48.5%, osteoporosis 23.5%). Reduced BMD before LT was not related to gender, underlying liver disease, or Child-Turcotte-Pugh classification. Body mass index (BMI) prior to LT, however, correlated significantly with the fracture risk. Alendronate prevented the ubiquitously observed bone loss after LT in patients with osteoporosis and osteopenia and, in addition, led to an increase in BMD in patients with osteoporosis within 24 months after LT. In conclusion, our study suggests that alendronate is efficacious in preventing the natural course of bone loss associated with LT.     

Bisphosphonates in the management of thalassemia-associated osteoporosis: a systematic review of randomised controlled trials

Bisphosphonates are potent inhibitors of bone resorption, widely used for the management of osteoporosis and fracture prevention. Recent evidence suggests that bisphosphonates may have beneficial effects in the treatment of thalassemia-associated osteoporosis, a complex and multifactorial condition. Here we summarise available data about the efficacy and tolerability of bisphosphonates in beta-thalassemic patients. Randomised controlled trials (RCTs) of bisphosphonates in beta-thalassemia were identified searching PubMed. Studies were reviewed to retrieve relevant clinical information. The following variables were considered to assess the safety and efficacy of bisphosphonates—bone mineral density (BMD), markers of bone turnover, incidence of fragility fracture, bone pain, back pain, and clinical adverse events. Five RCTs were identified, investigating alendronate, clodronate, zoledronic acid and neridronate. All bisphosphonates produced a significant decrease of the markers of bone turnover. Alendronate, neridronate, and zoledronic acid significantly improved BMD at the lumbar spine, femoral neck and total hip. Zoledronic acid and neridronate were also shown to reduce bone and back pain. Probably due to the small sample sizes and to the short duration of the trials, it was not possible to establish the anti-fracture efficacy of bisphosphonates; however, they were well tolerated and adverse events were rare but expected on the basis of previous studies. Sufficient evidence exists to support the use of bisphosphonates in the management of thalassemia-associated osteoporosis (to prevent bone loss and improve the BMD). Further research is warranted to establish their anti-fracture efficacy and long-term safety.     

唑来膦酸盐与骨质疏松症

目的 双膦酸盐是目前抗骨质疏松治疗最常用药物.唑来膦酸盐是每年1次静脉注射用双膦酸盐,探讨唑来膦酸盐对骨质疏松的治疗作用及安全性分析.方法 PubMed上检索应用唑来膦酸盐治疗骨质疏松及其他疾病的相关文献并进行分析.结果 HORIZON-PFT 3年研究表明唑来膦酸盐与安慰剂比较,能明显降低椎体、非椎体骨折风险,增加骨密度,降低骨转换标志物水平,增加骨小梁容量.在90 d内行髋部骨折外科治疗的患者中进行的HORIZON-RFT研究发现唑来膦酸盐与安慰剂比较能够明显降低再发骨折风险,降低全因死亡率,增加髋部及股骨颈骨密度.绝经后低骨密度妇女从阿伦膦酸钠改为唑来膦酸盐3个月内平均骨转换标志物水平先下降,后逐渐增至绝经前妇女正常范围,且可维持腰椎骨密度值12个月.另一研究表明与阿伦膦酸钠比较,唑来膦酸盐能更迅速的降低骨吸收标志物,抑制骨吸收.在安全性方面唑来膦酸盐可能的副作用包括急性一过性不良反应,如发热、肌痛、流感样症状,主要为轻到中度,常发生在静脉输注后3 d内,3～7 d左右缓解.研究表明唑来膦酸盐短期内可能引起肾功能的变化,但长期对肾功能未发现明显影响.颌骨骨质疏松性坏死可能与唑来膦酸盐相关,但发生率较低,且多发生在恶性肿瘤如多发性骨髓瘤和转移癌的患者中,尚未证实颌骨骨质疏松性坏死风险增高与用于治疗骨质疏松症批准剂量的唑来膦酸盐有关.其他少见的副作用包括房颤,无症状及一过性低钙血症,尚需要大样本长期研究证实.结论 每年1次唑来膦酸盐是治疗绝经后骨质疏松新的选择.     

Can long-term bisphosphonate use causes low-energy fractures? A case report

Bisphosphonates are inorganic pyrophosphate analog which accumulate on the bone surface, cause osteoclast apoptosis, and inhibit bone resorption. The nitrogen-containing bisphosphonates continue to be the drug of choice for the treatment of osteoporosis in both men and women. Although histomorphometric studies including bone biopsies have not shown any evidence of microcracks, recent studies have revealed that potent bisphosphonates are responsible for the oversuppression of bone turnover leading to microdamages, reduced bone strength, and increased fracture risk. There are individual cases reporting atypical femoral fractures and severely suppressed bone turnover along with long-term (≥5 years) use of biphosphonates. In this study, we report on a 74-year-old woman with a history of continuous alendronate use for nearly 16 years who presented to the emergency department with right proximal humerus and left femur fracture.     

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy

Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density (BMD) and decrease fracture risk in postmenopausal women with osteoporosis. This was a multicenter, international, randomized, double‐blind, double‐dummy study in 504 postmenopausal women ≥ 55 years of age with a BMD T‐score of ?2.0 or less and ?4.0 or more who had been receiving alendronate therapy for at least 6 months. Subjects received open‐label branded alendronate 70 mg once weekly for 1 month and then were randomly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12 months. Changes in BMD and biochemical markers of bone turnover were evaluated. In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month 12 compared with a 1.05% increase in subjects continuing on alendronate (p < .0001). Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius (all p < .0125). Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate (p < .0001) at all time points with denosumab. Adverse events and serious adverse events were balanced between groups. No clinical hypocalcemic adverse events were reported. Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups. Copyright © 2010 American Society for Bone and Mineral Research     

Factors associated with bisphosphonate treatment failure in postmenopausal women with primary osteoporosis

Summary

Among 97 postmenopausal women with primary osteoporosis, adequate calcium and vitamin D supplementation, and good compliance to a 36-month bisphosphonate treatment, the 25.8 % of patients are inadequate responders. Current smoking and a bone turnover in the upper part of the normal range increase the risk of treatment failure.

Introduction

To evaluate the prevalence of the bisphosphonate treatment failure and its possible associated factors in women with primary osteoporosis (PO).

Methods

We studied 97 previously untreated postmenopausal women with PO and fragility fractures and/or a FRAX® 10-year probability of a major osteoporotic fracture ≥7.5 %, before and after a 36-month treatment with alendronate or risedronate and adequate vitamin D supplementation with good compliance. At baseline and after 36 months, lumbar spine (LS) and femoral bone mineral density (BMD) were assessed by Dual X-ray absorptiometry and vertebral fractures by spinal radiographs. Spinal deformity index (SDI) was calculated. Treatment failure was defined by the presence of ≥2 incident fragility fractures and/or a BMD decrease greater than the least significant change.

Results

Bisphosphonate treatment failure was observed in 25.8 % of patients. Age, body mass index, years since menopause, familiar history of hip fracture, number of falls, type of bisphosphonate used, 25-hydroxyvitamin D levels (25OHVitD), BMD, SDI, and FRAX® score at baseline were not different between responders and inadequate responders. Treatment failure was associated with current smoking (OR 3.22, 95 % CI 1.10–9.50, P?=?0.034) and baseline alkaline phosphatase total activity levels ≥66.5 U/L (OR 4.22, 95 % CI 1.48–12.01, P?=?0.007), regardless of age, number of falls, LS BMD, and baseline SDI.

Conclusions

The 25.8 % of PO postmenopausal women inadequately responds to bisphosphonates, despite a good compliance to therapy and normal 25OHVitD levels. The current smoking and bone turnover in the upper part of the normal range are associated with the inadequate response to bisphosphonates.     

The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid

We investigated the effects of biologics for rheumatoid arthritis (RA) patients on bone mineral density (BMD) and bone metabolic markers (BMM), retrospectively, and also clarified the effects of bisphosphonates (alendronate or risedronate 35 mg/week) and glucocorticoids. Participants in this study comprised 219 patients with RA, including 117 patients treated with biologics (infliximab, n = 90; etanercept, n = 27) and 102 patients with conventional disease-modifying anti-rheumatic drugs (DMARDs) for 1 year. Changes in BMD at the lumbar spine and total hip and BMMs [urinary type I collagen cross-linked N-telopeptide (NTX) and bone-specific alkaline phosphatase] were measured. BMD of the lumbar spine in both groups and total hip BMD in the biologics group were unchanged during treatment with biologics. However, BMD of the total hip was significantly decreased in the DMARDs group (from 0.731 ± 0.135 to 0.706 ± 0.135 g/cm²). Patients receiving glucocorticoids without bisphosphonates showed significant decrease in BMD of the total hip compared with patients not receiving glucocorticoids or receiving glucocorticoids with bisphosphonates in both biologics and DMARDs groups. Furthermore, BMD of the lumbar spine increased (p < 0.05) for patients in the biologics group who received bisphosphonates. NTX was significantly decreased only in the biologics group. Multiple regression analysis showed that BMD and bone metabolic marker levels correlated positively with bisphosphonate and biologics use and negatively with glucocorticoid use. BMD of the total hip was maintained in the patients using biologics without glucocorticoids or with bisphosphonates, but it was not maintained in the DMARDs patients, even without glucocorticoids or with bisphosphonates. Even if biologics have protective effect against bone loss of RA patients, we should consider reducing the dose of glucocorticoids and adding bisphosphonates for the treatment of osteoporosis.     

Comparison of treatment effects of teriparatide and the bisphosphonate risedronate in an aged,osteopenic, ovariectomized rat model under various clinical conditions

Teriparatide and bisphosphonates are osteoporosis medications that increase bone mineral density (BMD) and prevent fracture, but each has a different mechanism of action. Teriparatide promotes bone formation, while bisphosphonates suppress bone resorption. In the clinical setting, however, drug selection is not always tailored to the particular clinical condition of the patient or mechanism of action of the drug. We compared the effects of teriparatide and the bisphosphonate risedronate on bone metabolism using two ovariectomized rat models to elucidate the optimal use of these two drugs in the clinical setting. We first performed dose-finding experiments to determine the equivalent effective doses of each drug (5.6 and 3.0 µg/kg for teriparatide and risedronate, respectively). We then compared the effects of these doses on bone metabolism after subcutaneous administration three times weekly for 4 months starting either the day after ovariectomy (preventive study) or 12 months after ovariectomy (therapeutic study). The increase in proximal tibial BMD under the physical conditions that increased bone turnover at 1 to 2 months after ovariectomy was greater in the risedronate group than in the teriparatide group. In contrast, the increases in lumbar vertebral BMD and bone strength under the physical conditions that significantly decreased BMD and bone strength at 12 months after ovariectomy were greater in the teriparatide group than in the risedronate group. The present study provides important information on the selection of antiosteoporotic drugs, including teriparatide and risedronate, in treatment protocols tailored to the clinical conditions of patients and drug mechanisms.     

A meta-analysis characterizing the dose–response relationships for three oral nitrogen-containing bisphosphonates in postmenopausal women

Summary

A meta-analysis of spine BMD dose–response relationships for alendronate, risedronate, and ibandronate was performed. Data from all three oral bisphosphonates conform to a log–linear relationship between dose and change in spine BMD relative to placebo at 1 year, with an incremental gain of about 1 % for each doubling of dose.

Introduction

Animal data suggesting differences in potency and differences in approved oral dosage strengths for alendronate, risedronate, and ibandronate in the treatment of osteoporosis raise questions about their dose–response relationships and relative potencies in humans.

Methods

A meta-analysis of dose–response relationships for spine BMD increases for these three bisphosphonates was performed using data from 21 placebo-controlled trials that collectively included over 13,000 patients on active treatment and over 8,000 on placebo.

Results

For alendronate over the range of 1 to 20 mg/day, there was a strong log–linear relationship between dose and the increase in spine BMD relative to placebo at 1 year (R ²?=?0.994 using sample-weighted means). For each doubling in alendronate dose, there was an incremental gain of about 1 % in spine BMD. On the same scale, risedronate and ibandronate are approximately equipotent to alendronate on a weight-for-weight basis. The increases in BMD efficacy with each doubling of dose are parallel for all three nitrogen-containing bisphosphonates (NCBPs).

Conclusions

All three NCBPs are approximately equipotent and exhibit a log–linear relationship between dose and the increase in spine BMD. Differences in efficacy between the available oral bisphosphonate regimens appear to be a function of dose rather than inherent differences in therapeutic potential.     

Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday

Summary

In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture.

Introduction

A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants.

Methods

Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday.

Results

A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean?±?SD age was 66.9?±?8.9 years and BMI 24.5?±?4.4 kg/m². Duration of bisphosphonate treatment was 5.2?±?2.3 years, and follow-up during holiday was 3.3?±?1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday.

Conclusions

BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients. Additional studies are needed to identify predictors of fracture incidence during a bisphosphonate holiday.

     

Bisphosphonates for prevention of osteopenia in kidney-transplant recipients: a systematic review of randomized controlled trials

Summary

We conducted a systematic review of randomized controlled trials (RCTs) of bisphosphonates for the prevention of osteopenia in kidney-transplant recipients. Bisphosphonates improved bone mineral density at the lumbar spine and femoral neck after 12 months. However, additional well-designed RCTs are required to determine the optimal treatment strategy.Osteopenic–osteoporotic syndrome is a bone complication of renal transplantation. Bisphosphonates, calcitonin, and vitamin D analogs may be used to prevent or treat osteoporosis or bone loss after renal transplantation. However, there is currently no widely recognized strategy for the prevention of corticosteroid-induced osteoporosis. This study aims to assess the available evidence to guide the targeted use of bisphosphonates for reducing osteoporosis and bone loss in renal-transplant recipients. We searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE for randomized controlled trials of bisphosphonates for osteoporosis or bone loss after renal transplantation. A total of 352 abstracts were identified, of which 55 were considered for evaluation and 9 were included in the final analysis. The primary outcome measure was change in the bone mineral density (BMD) of the lumbar spine and femoral neck after 12 months. Data extraction was performed independently by two investigators. BMD at the lumbar spine was improved after treatment with bisphosphonates [9 trials; 418 patients; weighted mean difference (WMD), 0.61; 95 % confidence interval (CI), 0.16–1.06]. Eight trials (406 patients) that reported changes in BMD at the femoral neck also showed improved outcomes after treatment with bisphosphonates (WMD, 0.06; 95 % CI, 0.03–0.09). Bisphosphonates improve BMD at the lumbar spine and femoral neck after 12 months in renal-transplant recipients.

     

Effects of combined therapy of alendronate and low-intensity pulsed ultrasound on metaphyseal bone repair after osteotomy in the proximal tibia of aged rats

Bisphosphonates and low-intensity pulsed ultrasound (LIPUS) are both known to maintain or promote callus formation during diaphyseal fracture healing. However, the effect of these treatments on the repair of metaphyseal fractures has not been elucidated. To evaluate the effects of bisphosphonates and/or LIPUS on cancellous bone healing, an osteotomy was performed on the proximal tibial metaphysis of 9-month-old Sprague–Dawley rats (n = 64). Treatment with alendronate (1 μg/kg/day), LIPUS (20 min/day), or a combination of both was administered for 2 or 4 weeks, after which changes in bone mineral density (BMD), bone histomorphometric parameters, and the rate of cancellous bony bonding were measured. Alendronate suppressed bone resorption parameters at 2 weeks (p = 0.019) and increased bone volume and BMD at 4 weeks (p = 0.034 and p = 0.008, respectively), without affecting bony bonding. LIPUS had no significant effect on any of the histomorphometric parameters at 2 or 4 weeks, but significantly increased in BMD at 4 weeks (p = 0.026) as well as the percentage of bony bonding at both 2 and 4 weeks (p < 0.01). The combined therapy also showed significantly increased BMD compared with the control group at 4 weeks (p = 0.010) and showed a trend toward increased bony bonding. In conclusion, alendronate and LIPUS cause an additive increase in BMD at the affected metaphysis: alendronate increases the bone volume at the osteotomy site without interrupting metaphyseal repair, whereas LIPUS promotes metaphyseal bone repair, without affecting bone histomorphometric parameters.     

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。     

Critical impact of patient knowledge and bone density testing on starting osteoporosis treatment after fragility fracture: secondary analyses from two controlled trials

Summary

Most patients are not treated for osteoporosis after their fragility fracture “teachable moment.” Among almost 400 consecutive wrist fracture patients, we determined that better-than-average osteoporosis knowledge (adjusted odds?=?2.6) and BMD testing (adjusted odds?=?6.5) were significant modifiable facilitators of bisphosphonate treatment while male sex, working outside the home, and depression were major barriers.

Introduction

In the year following fragility fracture, fewer than one quarter of patients are treated for osteoporosis. Although much is known regarding health system and provider barriers and facilitators to osteoporosis treatment, much less is understood about modifiable patient-related factors.

Methods

Older patients with wrist fracture not treated for osteoporosis were enrolled in trials that compared a multifaceted intervention with usual care controls. Baseline data included a test of patient osteoporosis knowledge. We then determined baseline factors that independently predicted starting bisphosphonate treatment within 1 year.

Results

Three hundred seventy-four patients were enrolled; mean age 64 years, 78 % women, 90 % white, and 54 % with prior fracture. Within 1 year, 86 of 374 (23 %) patients were treated with bisphosphonates. Patients who were treated had better osteoporosis knowledge at baseline (70 % correct vs 57 % for untreated, p?Conclusions The most important modifiable facilitators of osteoporosis treatment in patients with fracture were knowledge and BMD testing. Specifically targeting these two patient-level factors should improve post-fracture treatment rates.     

Anti-hip fracture efficacy of biophosphonates: a Bayesian analysis of clinical trials.

In postmenopausal women, the efficacy of bisphosphonates on hip fracture risk is not clear. This Bayesian meta-analysis quantitatively reviewed data from 12 randomized clinical trials with 18,667 patients and found that bisphosphonate treatment was associated with a reduced risk for hip fracture by 42%. INTRODUCTION: The efficacy of antiresorptive bisphosphonates therapy on reducing hip fracture is not clear, because evidence from randomized clinical trials (RCTs) is inconclusive. This study was undertaken to quantitatively assess the effect of bisphosphonates on hip fracture using literature review and meta-analysis. MATERIALS AND METHODS: Bayesian methods of meta-analysis were applied to synthesize data from 12 RCTs available between 1990 and 2004. The trials involved 18,667 postmenopausal women with low BMD or osteoporosis who have been followed or treated for between 1 and 4 years. The medications used were etidronate (two trials) alendronate (six trials), risedronate (three trials), and clodronate (one trial). The primary endpoint was the incidence of hip fracture. RESULTS: When data from all 12 studies were pooled, treatment with bisphosphonates was associated with a reduced risk for hip fracture by 42% (relative risk [RR], 0.58; 95% credible interval [CrI], 0.42-0.80). The absolute rate reduction was 52 hip fractures per 10,000 women (95% CrI, 4-110) for a period of 3-year treatment. The probability that bisphosphonates are better than placebo (in reducing hip fracture risk by at least 30%) was 0.90. CONCLUSIONS: In postmenopausal women with osteoporosis or low BMD, bisphosphonate treatment is associated with reduced risk of hip fracture.