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Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.

ABSTRACT: In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk.The aim of the study was to identify factors associated with greater efficacy during ZOL 5 mg treatment.We conducted a subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis.A single infusion of ZOL 5 mg or placebo was administered at baseline, 12, and 24 months.Primary endpoints were new vertebral fracture and hip fracture. Secondary endpoints were nonvertebral fracture and change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups were age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index, and concomitant osteoporosis medications.Greater ZOL induced effects on vertebral fracture risk were seen with younger age (treatment-by-subgroup interaction, P = 0.05), normal creatinine clearance (P = 0.04), and body mass index >or= 25 kg/m(2) (P = 0.02). There were no significant treatment-factor interactions for hip or nonvertebral fracture or for change in BMD.ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women, and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.

SUBMITTER: Eastell R

PROVIDER: S-EPMC5101059 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.

Eastell Richard R Black Dennis M DM Boonen Steven S Adami Silvano S Felsenberg Dieter D Lippuner Kurt K Cummings Steven R SR Delmas Pierre D PD Palermo Lisa L Mesenbrink Peter P Cauley Jane A JA

The Journal of clinical endocrinology and metabolism 20090630 9

<h4>Context</h4>In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk.<h4>Objective</h4>The aim of the study was to identify factors associated with greater efficacy during ZOL 5 mg treatment.<h4>Design, setting, and patients</h4>We conducted a subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women wit ...[more]

PMID: 19567517

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Project description:The objective of this study was to determine the effect of once-yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double-blind, placebo-controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15-minute intravenous infusion of zoledronic acid (5?mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were self-reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3-year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p?=?.0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p?=?.0017). In Cox proportional-hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR)?=?0.94, 95% confidence interval (CI) 0.90-0.99] or limited activity owing to back pain (RR?=?0.94, 95% CI 0.87-1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed-rest days owing to a fracture (RR?=?0.58, 95% CI 0.47-0.72) and 7 or more limited-activity days owing to a fracture (RR?=?0.67, 95% CI 0.58-0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once-yearly infusion with zoledronic acid over a 3-year period significantly reduced the number of days that patients reported back pain, limited activity owing to back pain, and limited activity and bed rest owing to a fracture.

Project description:BackgroundGenome-wide association studies (GWASs) routinely identify loci associated with risk factors for osteoporosis. However, GWASs with relatively small sample sizes still lack sufficient power to ascertain the majority of genetic variants with small to modest effect size, which may together truly influence the phenotype. The loci identified only account for a small percentage of the heritability of osteoporosis. This study aims to identify novel genetic loci associated with DXA-derived femoral neck (FNK) bone mineral density (BMD) and quantitative ultrasound of the heel calcaneus estimated BMD (eBMD), and to detect shared/causal variants for the two traits, to assess whether the SNPs or putative causal SNPs associated with eBMD were also associated with FNK-BMD.MethodsNovel loci associated with eBMD and FNK-BMD were identified by the genetic pleiotropic conditional false discovery rate (cFDR) method. Shared putative causal variants between eBMD and FNK-BMD and putative causal SNPs for each trait were identified by the colocalization method. Mendelian randomization analysis addresses the causal relationship between eBMD/FNK-BMD and fracture.ResultsWe identified 9,500 (cFDR < 9.8E-6), 137 (cFDR < 8.9E-4) and 124 SNPs associated with eBMD, FNK-BMD, and both eBMD and FNK-BMD, respectively, with 37 genomic regions where there was a SNP that influences both eBMD and FNK-BMD. Most genomic regions only contained putative causal SNPs associated with eBMD and 3 regions contained two distinct putative causal SNPs influenced both traits, respectively. We demonstrated a causal effect of FNK-BMD/eBMD on fracture.ConclusionMost of SNPs or putative causal SNPs associated with FNK-BMD were also associated with eBMD. However, most of SNPs or putative causal SNPs associated with eBMD were not associated with FNK-BMD. The novel variants we identified may help to account for the additional proportion of variance of each trait and advance our understanding of the genetic mechanisms underlying osteoporotic fracture.

Project description:BACKGROUND:Nutritional factors including vitamin D, magnesium, and fat are known to affect bone mineral accrual. This study aimed to evaluate associations between dietary nutrient intakes (both macronutrients and micronutrients) and bone mineral density (BMD) in children and adolescents. METHODS:Data for this cross-sectional, population-based study were derived from the National Health and Nutrition Examination Survey (NHANES). Participants aged from 8 to 19?years were included. The primary outcome was femoral neck BMD. RESULTS:Multivariate analyses revealed that for participants aged 8 to 11, daily sodium intake was significantly and positively associated with femoral neck BMD (B?=?0.9?×? 10-?5, p?=?0.031); in particular, subgroup analyses by sex found that in male participants aged 8-11, daily total cholesterol intake (B?=?5.3?×?10-?5, p?=?0.030) and calcium intake (B?=?-?2.0?×?10-?5, p?<?0.05) were significantly associated with femoral neck BMD in a positive and negative manner, respectively, but neither were observed in female participants of this age group. In contrast, daily intakes of vitamin D and magnesium were significantly and positively associated with femoral neck BMD in female participants aged 8-11 (B?=?246.8?×?10-?5 and 16.3?×?10-?5, p?=?0.017 and 0.033, respectively). For participants aged 16 to 19, daily total fat intake was significantly and negatively associated with femoral neck BMD (B?=?-?58?×?10-?5, p?=?0.048); further stratification by sex found that magnesium and sodium intakes were significantly and positively associated with femoral neck BMD only in females of this age group (B?=?26.9?×?10-?5 and 2.1?×?10-?5, respectively; both p?<?0.05). However, no significant associations between daily nutrient intakes and femoral neck BMD were identified in participants aged 12-15 before or after subgroup stratification. CONCLUSION:The study found that associations of specific nutrition-related variables with BMD of the femoral neck is dependent upon age and gender.

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Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.

Publications

Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.

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