Percentage Change In Bone Mineral Density Research Articles

Abatacept might increase bone mineral density at femoral neck for patients with rheumatoid arthritis in clinical practice: AIRTIGHT study

We investigated the influence of abatacept (ABT) on bone mineral density (BMD) and bone metabolic markers (BMMs) in patients with rheumatoid arthritis (RA) compared to other biologic disease-modifying anti-rheumatic drugs (bDMARDs). This prospective, comparative, non-randomized study (the AIRTIGHT study; UMIN000005570) investigated the effects of ABT and other bDMARDs on bone metabolism. A total of 165 RA patients were divided into ABT (n = 50) and non-ABT (n = 115). We evaluated percentage changes in BMD (%ΔBMD) at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Urinary levels of cross-linked N-telopeptide of type I collagen (uNTx) and bone-specific alkaline phosphatase (BAP) were used as markers of bone resorption and formation, respectively. No significant differences in 1-year completion rates were seen between ABT (64%) and non-ABT (72%; p = 0.387). The %ΔBMD at the femoral neck was significantly higher in the ABT group (0.97%) than in the non-ABT group (- 2.19%; p = 0.026). Whereas, no significant difference in %ΔBMD at the lumbar spine was observed between groups (ABT, - 0.40%; Non-ABT, - 1.67%; p = 0.524). No significant differences were observed in changes to uNTx or BAP. ABT treatment was significantly associated with increased BMD at the femoral neck (odds ratio (OR) 8.84; 95% CI 1.08-72.4; p = 0.04), and baseline lumbar osteoarthritis was significantly associated with BMD at the lumbar spine (OR 2.97; 95% CI 1.23-7.13; p = 0.02). The efficacy of ABT for increasing BMD at the femoral neck was superior to that of other bDMARDs. ABT may offer good efficacy for improving BMD at the femoral neck in patients with RA.

Short-term daily teriparatide in patients with rheumatoid arthritis

Objective: The aim of this study was to compare the efficacy of six-month teriparatide treatment followed by six-month bisphosphonate therapy with 12-month bisphosphonate monotherapy in Japanese rheumatoid arthritis (RA) patients who had not been previously treated for osteoporosis.Methods: A total of 34 RA patients with osteoporosis were enrolled. Thirteen patients received six-month teriparatide prior to six-month minodronate therapy (PTH group), and 21 patients received 12-month minodronate therapy (BP group). Bone mineral density (BMD), and bone turnover markers were measured prior to and 6 and 12 months after the initiation of treatment.Results: Bone mineral density of the spine was significantly increased after 12 months of treatment in both groups. In the PTH group, the mean percent change of BMD of the spine was significantly higher at 12 months after the initiation of treatment, as compared to the BP group (PTH group: 9.9 ± 1.5%, BP group: 5.5 ± 0.7%). Femoral neck BMD was significantly increased only in the PTH group after 12 months.Conclusion: Therapy involving six-month teriparatide followed by six-month minodronate therapy increased spine BMD to a greater degree than 12-month minodronate monotherapy. The strategy of short-term administration of teriparatide for RA patients with osteoporosis might be useful when additional bisphosphonate therapy is considered.

Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial.

NCT00867048. © 2017 American Society for Bone and Mineral Research.

Impact of Monthly 120 Mg Denosumab on Bone Metabolism in Bone-metastatic Prostate Cancer Undergoing Androgen Deprivation Therapy

Background: While semiannual 60 mg denosumab is a common treatment for osteoporosis, impact of monthly 120 mg denosumab, the common treatment protocol for bone metastases from solid tumors, on bone metabolism is unclear.Materials and Methods: We reviewed 15 patients with bone-metastatic prostate cancer who initiated monthly 120 mg denosumab in conjunction with androgen deprivation therapy between 2013 and 2014. Bone mineral density (BMD) was measured at lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA), before treatment and annually thereafter. Bone metabolism markers, including urine N-terminal telopeptide (uNTx) and bone type alkaline phosphatase (BAP), were monitored monthly.Results: Twelve of 15 (80%) patients had evaluable DXA before treatment, and of them, eight underwent DXA after a year of initiation without discontinuation of denosumab. Percent changes in BMD from baseline were +6.2% at lumbar spine and +7.6% at femoral neck, both of which were significant increases (both P<0.01). Bone metabolism markers were evaluable in 11 (73%) patients: uNTx decreased rapidly, while BAP declined gradually after initiating denosumab. These effects were similar to those seen by the standardized dose for osteoporosis in previous literature. There were no denosumab-related severe adverse events during the follow-up period. Conclusions: The impact of monthly 120 mg denosumab on bone metabolism was significant, but almost equivalent to that of the standard dose for osteoporosis (60mg semiannually) in bone-metastatic prostate cancer undergoing androgen deprivation therapy. Whereas the higher dose has reportedly reduced skeleton-related events, the effect on bone metabolism seemed plateaued or showed no dose-dependency.

Effect of denosumab on bone mineral density (T-score classification of −1.0 to −2.5) in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer.

552 Background: Adjuvant aromatase inhibitor (AI) therapy is well established in postmenopausal women with hormone receptor-positive breast cancer, but such therapy is associated with bone loss and increased fracture risk. Denosumab, a fully human monoclonal antibody against receptor of nuclear-κB ligand, was previously proven to protect against AI-induced bone loss. In Japan, however, the efficacy of denosumab in the treatment of AI-associated bone loss has not been proven in a prospective study. Methods: This non-randomized prospective study was conducted at four institutions in Japan. we prospectively evaluated the bone mineral density (BMD) of the lumbar spine and bilateral femoral neck in hormone-receptor positive clinical stageⅠ–ⅢA, postoperative postmenopausal breast cancer patients who were scheduled for treatment with AI as adjuvant endocrine therapy or during AI adjuvant therapy. They received supplemental calcium, vitamin D and subcutaneous denosumab 60mg (n=103) every six months. At enrollment, all patients were required to have evidence of low bone mass, excluding osteoporosis. The primary endpoint was percentage change in lumbar spine BMD from baseline to month 12. The secondary endpoint was percentage change in bilateral femoral neck BMD from baseline to month 12. This is the first trial where the right and left femoral neck BMD are measured separately. Results: We enrolled 103 patients between November, 2014 to October, 2016. At 12 months, lumber spine BMD increased by 4.7 %. The patients who were administered prior AI therapy (n=60) had a 4.8 % increase, and the patients without prior AI therapy (n=40) had a 4.6 % increase. At 12 months, the right and left femoral neck BMD increased by 2.9 % and 2.0 %, respectively. Hypocalcemia ≥ grade2, osteonecrosis of the jaw (ONJ) and non-traumatic clinical fracture were absent in this study. Conclusions: Twice-yearly treatment with denosumab was associated with consistently greater gains in BMD among Japanese women receiving adjuvant AI therapy, regardless of whether prior AI therapy was administered. Clinical trial information: UMIN000013863.

Treatments to Prevent Bone Loss in Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis.

Objective:We conducted a systematic review and meta-analysis of studies that evaluated the effect of hormonal therapy [estrogen therapy including oral contraceptive pills (OCP)] and bisphosphonates in preventing bone loss in patients with functional hypothalamic amenorrhea (FHA).Methods:We searched several electronic databases for controlled and noncontrolled studies that enrolled females of any age presenting with FHA (including athletic, weight loss, and stress-associated amenorrhea/oligomenorrhea) through 9 January 2017. The outcomes of interest were fractures and bone mineral density (BMD). Random effects meta-analysis was used to pool outcomes across studies expressed as weighted mean difference and 95% confidence interval (CI).Results:Nine studies reporting on 280 patients that received different hormonal therapies were included. We did not identify studies that evaluated bisphosphonates. Meta-analysis demonstrated a statistically significant increase in BMD of the lumbar spine in patients receiving hormonal therapy after a median follow-up of 12 months (weighted mean difference, 0.032 g/cm2; 95% CI, 0.017 to 0.047; percentage change in BMD, 3.30%; 95% CI, 1.74 to 4.86). There was no substantial effect of receiving hormonal therapy on BMD of the femoral neck, trochanteric region, Ward triangle, or total body BMD. The quality of evidence was low because of the high risk of bias, imprecision (small sample size), and indirectness (as BMD is a surrogate outcome). None of the studies reported the incidence of fractures.Conclusion:The current evidence does not support using hormonal therapy for the sole purpose of improving bone health in patients with FHA. There are no data about bisphosphonates in this population.

Quantitative analysis of efficacy and associated factors of calcium intake on bone mineral density in postmenopausal women

This paper aims to quantify the efficacy of calcium intake in preventing bone mineral density (BMD) decrease among postmenopausal women and to investigate the factors that may affect the efficacy. Comprehensive literature search was conducted in PubMed and EMBASE from January 2016. Placebo-controlled or no-treatment controlled randomized trials focused on calcium intake for the management of osteoporosis in postmenopausal women were included. The clinical and demographic characteristics of participants and efficacy data, defined as the mean percentage change of spine BMD (L2-L4) at each observation time point compared with that of baseline, were extracted from the studies. Model-based meta-analysis (MBMA) was used to describe the time course of BMD change by calcium intake and identify the related factors. This study includes 17 trials involving 2537 subjects. The results showed that a classic pharmacodynamic maximal effect (E max) model could describe the time course of BMD change by calcium intake. Using this model, we found that age and calcium intake dose were key factors affecting the efficiency and onset of BMD change. A 60-year-old woman administered with 800mg/day calcium can achieve a maximum BMD increasing rate of 2.38%, and the time to reach 50% of this maximum (known as onset time) was 9.44months. An increase of 0.0817% per year was noted in the maximal effect value for women aged between 50 and 83years. For calcium dose interval from 250 to 2000mg/day, the onset time was expressed as 9.44 × (dose/800)-1.33months. Two-year calcium intake of 700, 1200, and 2000mg/day resulted in a maximum efficacy of BMD of 68.0, 81.3, and 89.6%, respectively. This indicates that the final efficacy had already reached the plateau (>80% E max) under the 1200-mg/day dose. Calcium intake can effectively postpone the tendency of BMD decrease in postmenopausal women. An increased calcium dose contributes to the shortening of the onset time. Considering the drug-acting rate and safety into account, menopausal women can be administered with a rational dose of 1200mg/day to reduce bone loss.

The Effects of Transdermal Estrogen Delivery on Bone Mineral Density in Postmenopausal Women: A Meta-analysis.

Due to its minimal systematic adverse effects, transdermal estrogen is widely used for the prevention of osteoporosis in postmenopausal women. The present meta-analysis aimed to clarify the effects of transdermal estrogen on bone mineral density (BMD) of postmenopausal women. Studies were identified by searching electronic databases including Cochrane Library, MEDLINE, Embase , and CINAHL databases, and also the Sciences Citation Index. Systematic reviewof articles was published between January 1989 to February 2016.Reference lists of the included articles were also evaluated and consultations were made with relevant experts. While 132 studies included the desired keywords, only nine clinical trials met the inclusion criteria and were finally reviewed. The pooled percent change in BMD was statistically significant in favor of transdermal estrogen. According to resulting pooled estimate, lumbar spine BMD one and two years after transdermal estrogen therapy was respectively 3.4% (95% CI: 1.7-5.1) and 3.7% (95% CI: 1.7-5.7) higher than the baseline values. The test for heterogeneity was not statistically significant based on the I2 heterogeneity index. One-two years of transdermal estrogen delivery can effectively increase BMD and protect the bone structure in postmenopausal women.

Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial

ObjectiveTo assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis). Patients and MethodsACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients. ResultsOf 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012. These results are from a prespecified 6-month interim analysis (cutoff date, June 2, 2015); the study is ongoing. Findings indicated percentages of patients with new morphometric vertebral fractures: PBO/ALN, 4.4% vs ABL-SC/ALN, 0.55%; relative risk reduction, 87% (relative risk, 0.13; 95% CI, 0.04-0.41; P<.001). Kaplan-Meier estimated rates of nonvertebral fractures were PBO/ALN, 5.6% vs ABL-SC/ALN, 2.7%; risk reduction, 52% (hazard ratio [HR], 0.48; 95% CI, 0.26-0.89; log-rank P=.02). There was also a 58% risk reduction of major osteoporotic fractures (HR, 0.42; 95% CI, 0.21-0.85; log-rank P=.01) and a 45% risk reduction of clinical fractures (HR, 0.55; 95% CI, 0.33-0.92; log-rank P=.02) in the ABL-SC/ALN group vs the PBO/ALN group. At 25 months, bone mineral density percentage change from ACTIVE baseline for ABL-SC/ALN vs PBO/ALN was as follows: lumbar spine, 12.8%; total hip, 5.5%; femoral neck, 4.5% vs 3.5%, 1.4%, 0.5%, respectively (group differences at all sites P<.001). ConclusionUse of ABL-SC for 18 months followed by ALN for 6 months improved bone mineral density and reduced fracture risk throughout the skeleton and may be an effective treatment option for postmenopausal women with osteoporosis. Trial Registrationclinicaltrials.gov Identifier: NCT01657162.

The effect of sequential therapy for postmenopausal women with osteoporosis: A PRISMA-compliant meta-analysis of randomized controlled trials.

Osteoporosis, more likely to occur in postmenopausal women, is a chronic condition that usually requires a long-term treatment strategy, but the use of either antiresorptive or anabolic drugs should be limited to 18 to 24 months. Discontinuing antiosteoporosis drugs may result in rapidly declining bone mineral density (BMD). Therefore, many patients are treated with the sequential use of 2 or more drugs. However, whether switching treatment from anabolic to antiresorptive drugs or the reverse could maintain or further increase BMD; and whether the sequential therapy could outperform the monotherapy under the same treatment duration still remains unclear. Nowadays, no firm conclusions were drawn. We searched Medline, Embase, and Cochrane Library from January 1, 1974 until February 1, 2016 to identify all randomized controlled trials for evaluating the effectiveness of sequential therapy of antiresorptive and anabolic drugs in postmenopausal osteoporosis women with the BMD changes of lumbar spine, femoral neck, and total hip as the outcomes. We evaluated the methodological quality and abstracted relevant data according to the Cochrane Handbook. Eight trials involving 1509 patients were included. The pooled data showed that after switching treatment, the alternative drugs maintained the BMD and significantly increased the percentage change in BMD at the lumbar spine (MD, 3.59; 95% CI, 2.26-4.93), femoral neck (MD, 1.44; 95% CI, 0.60-2.27), and total hip (MD, 1.24; 95% CI, -0.12 to 2.60), although change in BMD was not significantly increased at the total hip. The sequential therapy significantly increased BMD from baseline at the lumbar spine (SMD, 0.59; 95% CI, 0.26-0.91), femoral neck (SMD, 0.22; 95% CI, 0.06-0.37), and total hip (SMD, 0.28; 95% CI, 0.01-0.56). After switching treatment, sequential therapy further increased BMD. The sequential therapy showed a more significant improvement in BMD compared with any anti-resorptive drug given for the same treatment duration and was as effective as anabolic drugs. Thus, sequential therapy may be recommended as an effective treatment for osteoporotic women. However, more randomized controlled trials are still needed to determine the best sequence and the most appropriate drugs of sequential therapy.

Effectiveness of elcatonin for alleviating pain and inhibiting bone resorption in patients with osteoporotic vertebral fractures.

Elderly patients with osteoporotic vertebral fractures often experience severe pain that reduces their quality of life (QOL). Calcitonin, a bone resorption inhibitor, has been reported to alleviate pain in such patients; however, few clinical studies have demonstrated this effect. The objective of this study was to compare changes in pain scores, activities of daily living (ADL), QOL, bone resorption, bone mineral density (BMD), and fracture healing among patients with new vertebral fractures who received different treatment modalities. We conducted an open-label, multicenter, randomized, parallel control group study comprising 107 female patients ≥55years old with acute back pain from vertebral fracture. All subjects received either intramuscular injections of elcatonin, a derivative of calcitonin, or an oral nonsteroidal antiinflammatory drug (NSAID) combined with an active vitamin D3 (VD3) analogue for 6months. The pain was assessed using a visual analogue scale, and ADL and QOL were assessed using questionnaires. BMD was measured using dual-energy X-ray absorptiometry. A two-tailed significance level of 5% was used. The elcatonin IM group had significantly higher QOL score at 2weeks and later, and significantly lower VAS and ADL scores than those in the NSAID+VD3 group at 1month and later. The elcatonin IM group had significantly reduced TRACP-5b levels compared with those in the NSAID+VD3 group at 3months and later and significantly higher percent changes in BMD than the NSAID+VD3 group. These results suggest that elcatonin significantly alleviated pain, inhibited bone resorption, and improved ADL, QOL, and BMD compared with NSAID+VD3.

Bone Mineral Density and Weight Changes in Adolescents Randomized to 3 Doses of Depot Medroxyprogesterone Acetate

Study ObjectiveTo assess the association between medroxyprogesterone acetate exposure and bone mineral density (BMD) loss and weight change in adolescents. DesignForty-eight-week prospective, randomized trial conducted May 2012-April 2014. SettingRecruitment occurred in the general community and outpatient clinics in central Ohio. ParticipantsSelf-referred sample of 34 female adolescents aged 12-21 years initiating depot medroxyprogesterone acetate (DMPA). InterventionsRandomization to 1 of 3 DMPA doses (150, 104, or 75 mg) given intramuscularly every 12 weeks for 48 weeks. Main Outcome MeasuresAbsolute and percent change in BMD from 0-48 weeks at the L1-L4 lumbar spine, total hip, and femoral neck; absolute and percent change in weight at 48 weeks. ResultsDMPA dose was associated with medroxyprogesterone acetate exposure as evidenced by a direct relationship (P < .001) between dose group and area under the concentration time curve. At 48 weeks, no significant BMD decreases were seen in the 75 mg dose group. The 104 and 150 mg dose groups experienced significant (P < .01) decreases in L1-L4 lumbar spine BMD (3.1% and 4.0%, respectively). The 150 mg group also had significant (P < .05) decreases in total hip (3.0%) and femoral neck (4.0%) BMD. No group differences in weight change were observed. No pregnancies occurred in any DMPA dose group. ConclusionsOur data provide evidence of a dose-response relationship between DMPA and BMD loss. Intramuscular DMPA doses less than 150 mg can decrease risk of BMD loss in adolescents. The risk/benefit ratio of lower-dose DMPA should be further investigated in larger and more diverse adolescent populations.

A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax® and Fosamax® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel® and Actonel Once a Week®, Warner Chilcott UK Ltd), ibandronic acid (Bonviva®, Roche Products Ltd) and zoledronic acid (Aclasta®, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty. Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX. We assumed that all treatment strategies are viable alternatives across the whole population. Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. This study is registered as PROSPERO CRD42013006883. The National Institute for Health Research Health Technology Assessment programme.

Efficacy of alfacalcidol and alendronate on lumbar bone mineral density in osteoporotic patients using proton pump inhibitors.

It has been indicated that proton pump inhibitor (PPI) use is associated with a loss of the anti-fracture efficacy of alendronate (AD). However, there are few prospective studies that have investigated the efficacy of AD on lumbar bone mineral density (BMD) in osteoporotic patients who are using PPIs. Thus, the aim of the present study was to investigate the efficacy of alfacalcidol (AC) and AD on lumbar BMD in osteoporotic patients using PPIs. A prospective, randomized, active control study enrolled such osteoporotic patients (age, ≥50 years). The patients were randomly assigned to receive AC (1 µg/day) or AD (35 mg/week) and were followed up for one year. Patient profiles were maintained, and lumbar BMD, bone-specific alkaline-phosphatase (BAP) and collagen type-I cross-linked N-telopeptide (NTX), upper gastrointestinal endoscopy results, and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) were evaluated. Percentage changes in lumbar BMD, NTX, BAP, and change in FSSG score from baseline to the end of one year of treatment were investigated. Sixteen patients were eligible for analysis (eight assigned to receive AC, eight assigned to receive AD). The percentage change in lumbar BMD from baseline to the end of treatment was −0.4±4.0% for the AC group vs. 6.8±6.3% for the AD group (P=0.015). No significant percentage change of BAP and NTX between the two groups was observed. Subsequent to one year of treatment, the FSSG score did not change from the baseline values for either study group, and no new bone fractures or esophagitis were observed in either group of patients. The findings demonstrated that in osteoporotic patients using concomitant PPIs, there was a greater increase in lumbar BMD after one year of treatment with AD compared with AC. However, the number of study subjects was small; thus, further, large prospective studies are required to determine the effect of AD in osteoporotic patients using concomitant PPIs.

Clinical effectiveness of bisphosphonates for the prevention of fragility fractures: A systematic review and network meta-analysis

ObjectivesTo assess the relative efficacy of bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid) for the treatment of osteoporosis using network meta-analysis (NMA). MethodsA systematic review of the literature was conducted using PRISMA guidelines. A network meta-analysis was used to determine the relative efficacy of treatments on four fracture outcomes (vertebral, non-vertebral, hip and wrist) and percentage change in femoral neck bone mineral density (BMD). Treatment effects were modelled using an exchangeable treatment effects model. Heterogeneity in treatment effects was explored by considering potential treatment effect modifiers using meta-regression. Where appropriate, inconsistency between direct and indirect evidence was assessed using node-splitting. Results46 randomised controlled trials (RCTs) were identified. Twenty seven RCTs provided fracture data and 35 RCTs provided BMD data for analysis. Zoledronic acid was associated with the greatest treatment effect on vertebral fractures (HR 0.41, 95% CrI: 0.28, 0.56) and percentage change in BMD (3.21, 95%: CrI 2.52, 3.86) compared to placebo. The greatest treatment effect on non-vertebral and wrist fractures was given by risedronate (HR 0.72, 95%: CrI 0.53, 0.89 and HR 0.77, 95%: CrI 0.44, 1.24, respectively). For hip fractures the greatest treatment effect was given by alendronate (HR 0.78, 95% CrI: 0.44, 1.30). ConclusionsAll treatments examined were associated with beneficial effects on fractures and femoral neck BMD relative to placebo. For vertebral fractures and percentage change in femoral neck BMD the treatment effects were statistically significant for all treatments. Pairwise comparisons between treatments indicated that no active treatment was statistically significantly more effective than any other active treatment for fracture outcomes. There was some heterogeneity in treatment effects between studies suggesting differential treatment effects according to study characteristics; however, there was no evidence of differential treatment effects with respect to gender and age.

Alendronate prevents glucocorticoid-induced osteoporosis in patients with rheumatic diseases: A meta-analysis.

Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a bisphosphonate, has been recommended in the prevention of GIOP. However, the efficacy and safety of alendronate in preventing GIOP remains controversial. We performed a meta-analysis to investigate the efficacy and safety of alendronate in preventing GIOP in patients with rheumatic diseases.We retrieved randomized controlled trials from PubMed, EMBASE, and the Cochrane Library. Two reviewers extracted the data and evaluated the risk of bias and quality of the evidence. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes, and the mean difference (MD) with a 95% CI for continuous outcomes using Review Manager, version 5.3.A total of 339 studies were found, and 9 studies (1134 patients) were included. Alendronate was not able to reduce the incidence of vertebral fractures (RR = 0.63, 95% CI: 0.10-4.04, P = 0.62) and nonvertebral fractures (RR = 0.40, 95% CI: 0.15-1.12, P = 0.08). Alendronate significantly increased the percent change in bone mineral density (BMD) at the lumbar spine (MD = 3.66, 95% CI: 2.58-4.74, P < 0.05), total hip (MD = 2.08, 95% CI: 0.41-3.74, P < 0.05), and trochanter (MD = 1.68, 95% CI: 0.75-2.61, P < 0.05). Significant differences were not observed in the percent change in BMD at the femoral neck (MD = -0.33, 95% CI: -2.79 to 2.13, P = 0.79) and total body (MD = 0.64, 95% CI: -0.06 to 1.34, P = 0.07). No significant differences in the adverse events were observed in patients treated with alendronate versus the controls (RR = 1.00, 95% CI: 0.94-1.07, P = 0.89). The odds of gastrointestinal adverse events were significantly reduced (RR = 0.77, 95% CI: 0.62-0.97, P < 0.05).Our analysis suggests that alendronate can increase the percent change in BMD at the lumbar spine, total hip, and trochanter, and is not associated with an increased incidence of gastrointestinal adverse events; however, the vertebral and nonvertebral fractures cannot be reduced. However, the results should be interpreted with caution due to the poor statistical power.

Change in bone mineral density during adjuvant chemotherapy for early-stage breast cancer

PurposeAdjuvant chemotherapy has been associated with loss of bone mineral density (BMD) either as a direct effect or due to glucocorticoids used as supportive care medication. A prospective cohort study was conducted to evaluate changes in BMD from baseline to right after completion of chemotherapy, i.e., 4 months.MethodsDual-imaging X-ray absorptiometry (DXA) was performed at baseline and after completing anthracycline- and taxane-based chemotherapy to measure BMD in the spine, hip, and forearm in early-stage breast cancer patients. High-dose prednisolone was used at three weekly intervals to reduce nausea and vomiting. Patients were advised a daily calcium/vitamin D supplement. Linear regression was used to assess mean percentage change in BMD and 95 % confidence intervals (95 % CI) according to doses of prednisolone, menopausal status, smoking, and BMI.ResultsEight patients were excluded: seven because of initiation of bisphosphonate treatment due to osteoporosis at baseline, and one had non-interpretable DXA. The final cohort included 97 patients with a mean age of 53 years (range 34–72). Mean cumulative prednisolone dose was 1308 mg (95 % CI 1255; 1362). BMD increased 1.36 % (95 % CI 0.7; 2.0, p < 0.001) in the spine and 1.27 % (95 % CI 0.9; 1.7, p < 0.001) in the hip. Forearm BMD did not change. Postmenopausal women had increases in spine BMD of 2.35 % (95 % CI 1.1; 3.6, p < 0.001) compared to premenopausal women. The spine BMD of current smokers decreased 1.67 % (95 % CI −3.3; −0.1, p = 0.04) compared to never/former smokers.ConclusionsAdjuvant chemotherapy supplemented with prednisolone was not associated with loss of BMD. Postmenopausal women gained bone mass, whereas current smokers lost bone mass.

Evaluation of efficacy and safety of conjugated estrogens/bazedoxifene in a Latin American population

Introduction Conjugated estrogens/bazedoxifene (CE/BZA) relieves menopausal symptoms and increases bone mineral density (BMD).Objective To evaluate CE/BZA in a Latin American subpopulation from randomized, double-blind, phase-3, multinational trials.Methods Safety data were pooled from three trials from non-hysterectomized postmenopausal Latin American women assigned to CE 0.45 mg/BZA 20 mg (n = 227), CE 0.625 mg/BZA 20 mg (n = 222), or placebo (n = 193). Efficacy outcomes from one study included changes in hot flush frequency at week 12 in women with at least seven moderate/severe hot flushes/day or 50/week at baseline (n = 39), and from baseline to month 12 for BMD (n = 381) and genitourinary syndrome of menopause (GSM) (women with baseline GSM; n = 189).Results At week 12, women taking CE/BZA had four to five fewer moderate/severe hot flushes/day vs. placebo. At month 12, percentage changes in BMD with CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, and placebo were 1.2%, 1.6%, and –1.1% for lumbar spine and 1.1%, 1.2%, and –0.3% for total hip. GSM improved with treatment (percentage superficial cells: 4.5, 7.4, vs. 2.0; percentage parabasal cells: –9.3, –27.8 vs. 2.8). There were no new/unexpected safety trends.Conclusion CE/BZA improved vasomotor symptoms, GSM, and BMD in Latin American women, with efficacy/safety similar to the global population.

Association Between Geranylgeranyl Pyrophosphate Synthase Gene Polymorphisms and Bone Phenotypes and Response to Alendronate Treatment in Chinese Osteoporotic Women.

Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase (GGPPS) gene polymorphisms and bone response to alendronate in Chinese osteoporotic women.Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose (70 mg per two weeks) or standard dose (70 mg weekly) of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density (BMD), serum cross-linked C-telopeptide of type I collagen (β-CTX), and total alkaline phosphatase (ALP) were measured before and after treatment. GGPPS gene polymorphisms and the changes of BMD and bone turnover markers after treatment were analyzed.Results rs10925503 polymorphism of GGPPS gene was correlated to serum β-CTX levels at baseline, and patients with TT genotype had significantly higher serum β-CTX level than those with TC or CC genotype (all P<0.05). No correlation was found between polymorphisms of GGPPS gene and serum total ALP levels, as well as BMD at baseline. After 12 months of treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly (P<0.01), and without obvious differences between the low dose and standard dose groups (all P>0.05). However, GGPPS gene polymorphisms were uncorrelated to percentage changes of BMD, serum total ALP, and β-CTX levels (all P>0.05).Conclusion GGPPS gene polymorphisms are correlated to osteoclasts activity, but all tag single nucleotide polymorphisms of GGPPS gene have no influence on the skeletal response to alendronate treatment.

Bone Mineral Density Changes Among Young, Healthy African Women Receiving Oral Tenofovir for HIV Preexposure Prophylaxis.

Background:Limited data exist on effect of tenofovir disoproxil fumarate (TDF) when used for preexposure prophylaxis (PrEP) on bone mineral density (BMD) in HIV-negative women. We evaluated the effect of daily oral TDF and emtricitabine/TDF compared with placebo on BMD among women enrolled in an HIV-1 PrEP trial.Methods:HIV-uninfected women in Uganda and Zimbabwe had BMD measurements of lumbar spine (LS) and total hip (TH) by dual-energy x-ray absorptiometry at baseline and every 24 weeks for 48 weeks of active treatment and for 48 weeks after discontinuation of study medication. Plasma tenofovir levels were assessed every 12 weeks for the first 48 weeks.Results:Of 518 women enrolled, 432 had dual-energy x-ray absorptiometry results at baseline and week 48. In the primary analysis, no significant differences in percent BMD change in hip or spine between arms observed, likely because of low product adherence. Among the subset with tenofovir detection in 75%–100% of plasma samples, the mean percent BMD change from baseline to week 48 in the LS was 1.4% lower for TDF or emtricitabine/TDF recipients than for placebo (P = 0.002) and TH BMD was 0.9% lower (P = 0.018). BMD changes from end of active treatment to 48 weeks were significantly greater in the active arm participants compared with placebo participants with a net difference of approximately +0.9% at the LS (P = 0.007) and +0.7% (P = 0.003) at the TH.Conclusions:TDF-containing oral PrEP resulted in small but significant reversible decreases in hip and spine BMD among young African women.