Prediction of changes in bone mineral density in postmenopausal women treated with once-weekly bisphosphonates.
ABSTRACT In clinical practice, bone mineral density (BMD) determined by dual-energy x-ray absorptiometry is used to monitor response to osteoporosis therapy. However, 1 to 2 yr are usually required to assess patients' BMD responses. The possibility of earlier indicators of a response or nonresponse to treatment, such as changes in bone turnover markers (BTMs), is of interest to physicians and patients.
In this post hoc analysis of women treated with once-weekly bisphosphonates, we examined the association of tertile percentage change from baseline in BTMs at 3 or 6 months and association of several baseline clinical characteristics with 24-month percentage change from baseline in BMD and with percentage of patients showing BMD nonresponse (defined as BMD loss at two or more of four sites) at 24 months. Multivariable analysis was performed to determine which factors were independently associated with BMD nonresponse.
Patients in the tertile with the greatest decrease in each of the BTMs had the greatest mean increase in BMD and the lowest percentage of BMD nonresponders at 24 months. Several characteristics were independently associated with BMD nonresponse, including smaller 3-month reductions from baseline in serum C-terminal telopeptide of type 1 collagen, bone-specific alkaline phosphatase, and N-terminal propeptide of type 1 procollagen; younger age of menopause; a family history of osteoporosis; and higher baseline trochanteric BMD. Baseline BTMs were not predictive of 24-month BMD response to therapy. The strongest associations were for changes in BTMs with treatment.
In groups of patients, short-term changes in markers of bone turnover appear to be predictors of longer term BMD response and nonresponse to bisphosphonate therapy.
- [Show abstract] [Hide abstract]
ABSTRACT: There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax(®), MSD), risedronate (Actonel(®), Warner Chilcott Company), zolendronate (Zometa(®), Novartis)], raloxifene (Evista(®), Eli Lilly and Company Ltd), strontium ranelate (Protelos(®), Servier Laboratories Ltd), denosumab (Prolia(®), Amgen Ltd) or teriparatide (Forsteo(®), Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs and outcome measures were eligible. The development of a decision model was planned to determine the cost-effectiveness of bone turnover markers for informing changes in patient management if clinical effectiveness could be established. Forty-two studies (70 publications) met the inclusion criteria; none evaluated cost-effectiveness. Only five were randomised controlled trials (RCTs); these assessed only the impact of bone marker monitoring on aspects of adherence. No RCTs evaluated the effectiveness of bone turnover marker monitoring on treatment management. One trial suggested that feedback of a good response decreased non-persistence [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.95], and feedback of a poor response increased non-persistence (HR 2.22, 95% CI 1.27 to 3.89); it is not clear whether or not the trial recruited a population representative of that seen in clinical practice. Thirty-three studies reported results of some assessment of test accuracy, mostly correlations between changes in bone turnover and bone mineral density. Only four studies reported on intra- or interpatient reliability and reproducibility in treated patients. Overall, the results were inconsistent and inconclusive, owing to considerable clinical heterogeneity across the studies and the generally small sample sizes. As clinical effectiveness of bone turnover monitoring could not be established, a decision-analytic model was not developed. There was insufficient evidence to inform the choice of which bone turnover marker to use in routine clinical practice to monitor osteoporosis treatment response. The research priority is to identify the most promising treatment-test combinations for evaluation in subsequent, methodologically sound, RCTs. In order to determine whether or not bone turnover marker monitoring improves treatment management decisions, and ultimately impacts on patient outcomes in terms of reduced incidence of fracture, RCTs are required. Given the large number of potential patient population-treatment-test combinations, the most promising combinations would initially need to be identified in order to ensure that any RCTs focus on evaluating those strategies. As a result, the research priority is to identify these promising combinations, by either conducting small variability studies or initiating a patient registry to collect standardised data. The National Institute for Health Research Health Technology Assessment programme.Health technology assessment (Winchester, England). 02/2014; 18(11):1-180.
- [Show abstract] [Hide abstract]
ABSTRACT: Some patients experience reduced bone mineral density (BMD) despite bisphosphonate therapy. We performed a retrospective chart review study to detect factors associated with decreased BMD in men prescribed alendronate. Two investigators reviewed eligible medical records and used a standardized form to record potential characteristics predicting men's response to alendronate. We analyzed patient characteristics associated with annualized change in hip and spine BMD (D-BMD). Among 115 eligible men, 19 (17 %) experienced significantly decreased BMD at the hip or spine, defined as a change exceeding precision error. Eleven men (10 %) fractured during therapy. Spine D-BMD was positively associated with adherence to alendronate (R = 0.23, p = 0.02) and inversely associated with baseline body weight (R = -0.21, p = 0.03). Hip D-BMD was positively associated with annualized weight change (R = 0.19, p = 0.0498) and negatively associated with patient age and number of concomitant medications (R = -0.21, p = 0.03; R = -0.20, p = 0.03, respectively). In stepwise linear models, spine D-BMD was associated positively with alendronate adherence and multivitamin use and negatively with baseline body weight. Hip D-BMD was negatively associated with age. Fracture during treatment was associated with fracture prior to therapy (p = 0.03). In this small study of men prescribed alendronate, BMD response showed a positive association with adherence to therapy, weight gain, and use of a multivitamin. By contrast, older age, higher baseline body weight, and higher number of medications were each associated with a decrease in BMD. Larger studies are needed to confirm and extend these findings.Calcified Tissue International 03/2013; · 2.75 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The clinical profile of ibandronate as add-on to calcitriol and calcium was studied in this double-blind, placebo-controlled trial of 129 renal transplant recipients with early stable renal function (≤ 28 days posttransplantation, GFR ≥ 30 mL/min). Patients were randomized to receive i.v. ibandronate 3 mg or i.v. placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d. At baseline, 10 weeks and 12 months bone mineral density (BMD) and biochemical markers of bone turnover were measured. The primary endpoint, relative change in BMD for the lumbar spine from baseline to 12 months was not different, +1.5% for ibandronate versus +0.5% for placebo (p = 0.28). Ibandronate demonstrated a significant improvement of BMD in total femur, +1.3% versus -0.5% (p = 0.01) and in the ultradistal radius, +0.6% versus -1.9% (p = 0.039). Bone formation markers were reduced by ibandronate, whereas the bone resorption marker, NTX, was reduced in both groups. Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile, virtually maintaining BMD without any loss over 12 months after renal transplantation, whereas adding ibandronate significantly improved BMD in total femur and ultradistal radius, and also suppressed biomarkers of bone turnover. Ibandronate was also well tolerated.American Journal of Transplantation 09/2012; · 6.19 Impact Factor