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Combination therapy for osteoporosis: a reappraisal.

ABSTRACT: Combinations of anabolic and antiresorptive agents have potential to improve bone density and bone strength more than either agent alone. A large number of relatively small clinical trials have been performed evaluating combinations of PTH1-34 or PTH1-84 with a variety of antiresorptives, including hormone/estrogen therapy, raloxifene, alendronate (Aln), risedronate, ibandronate, zoledronic acid and denosumab (Dmab). Most of the studies evaluate dual-X-ray densitometry outcomes, with a few trials reporting volumetric bone mineral density (BMD) by quantitative computed tomography followed by finite element modeling of bone strength. None of the studies has been powered to assess differences in fracture incidence between combination therapy and monotherapy. BMD outcomes vary depending on the timing of introduction of the anabolic agent (before, during or after antiresorptive treatment), as well as according to the specific anabolic and antiresorptive used. Furthermore, effects of combination therapies are site dependent. The most consistent effect of combining antiresorptive agents with parathyroid hormone (PTH) is a superior hip BMD outcome compared with PTH alone. This is most evident when PTH is combined with a bisphosphonate or Dmab. In contrast to findings in the hip, in the majority of studies there is no benefit to spine BMD with combination therapy when compared with monotherapy. The two exceptions to this are when PTH is combined with Dmab and when PTH is given as monotherapy first for 9 months followed by the addition of Aln and continuation of PTH as combination treatment. On the basis of what we now know, in patients on bisphosphonates who suffer hip fractures or who have very low hip BMD, strong consideration should be given to starting teriparatide and continuing a bisphosphonate (possibly switching to zoledronic acid or even Dmab) to maximize hip BMD and strength. Furthermore, in treatment-naive individuals with very severe osteoporosis, such as those with spine and hip fractures, combination therapy with PTH and Dmab or PTH followed by combination treatment with a potent bisphosphonate or Dmab should be considered to maximize early increases in BMD.

SUBMITTER: Cosman F

PROVIDER: S-EPMC4007166 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Project description:BackgroundAccording to the mechanisms of action, combination therapy of anabolic and antiresorptive agents may produce more effect for the treatment of osteoporosis. However, the combination therapy of anabolic agents and bisphosphonates reports no benefit and even reduced the anabolic effects of anabolic agents. This study aims to assess the effect of combination therapy of anabolic and nonbisphosphonates antiresorptive agents in adults with osteoporosis.MethodsMedline, EMBASE, and Cochrane Library were searched from January 1, 1980 to November 1, 2017 for randomized controlled trials (RCTs) of adults with osteoporosis treated in combination therapy of anabolic and nonbisphosphonates antiresorptive agents compared with monotherapy of either agent alone. The primary outcome was the incidence of fractures. The secondary outcomes were the bone mineral density (BMD) changes at lumbar spine and total hip. Continuous outcomes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI), while dichotomous outcomes were expressed as risk ratio (RR) and 95% CI. The meta-analysis was performed using a random-effects model. I statistic (I?>?50% as a threshold indicates significant heterogeneity) was used to assess the heterogeneity.ResultsA total of 10 trials with a total of 1042 patients were included. The pooled results showed that the combination therapy demonstrated a significant advantage over a monotherapy in the BMD improvement at the lumbar spine (SMD 1.18; 95% CI, 0.63 to 1.72; I?=?93%) and the total hip (SMD 0.89; 95% CI, 0.48 to 1.29; I?=?88%) and further reduce the fracture risk (RR, 0.45; 95%CI, 0.21 to 0.94; I?=?0%).ConclusionsLow-to-moderate-quality evidence shows that the combination therapy of anabolic and nonbisphosphonates antiresorptive agents is superior to monotherapy in improving the BMD and reducing the fracture risk. However, further high methodological quality studies are needed to determine the antifracture efficacy, cost-effectiveness and safety of this strategy of combination therapy.

Project description:We investigated reasons for non-treatment of osteoporosis and discontinuation of osteoporosis therapy. Barriers to treatment include patients' preference for alternative treatments and a fear of possible side effects. Side effects are a common reason for treatment discontinuation, and they may be associated with a lack of willingness to restart treatment.Purpose/introductionOsteoporosis patients commonly cite treatment-related side effects, or the fear thereof, as a reason for discontinuing or not initiating anti-osteoporosis medications. The purpose of this study was to investigate, from the patient's perspective, reasons for (i) non-treatment of osteoporosis and (ii) discontinuation of osteoporosis therapy.MethodsThis was an internet-based survey of postmenopausal women in the USA who self-reported having been diagnosed with osteoporosis. Respondents were recruited from consumer research panels and received nominal compensation.ResultsWithin the surveyed population (N = 1407), 581 patients were currently being treated, 503 had never been treated, and 323 had previously been treated. Among patients never treated for osteoporosis, the highest ranking reasons for non-treatment were the use of alternative treatments such as over-the-counter vitamins/supplements (57.5 % of respondents) and fear of side effects (43.9 %). Among previously treated patients, frequent reasons for discontinuation included the direction of the physician (41.2 % of respondents), concerns about long-term safety (30.3 %), and the experience of side effects (29.8 %). When asked about their willingness to restart their osteoporosis medication, previously treated patients who were not willing (N = 104) to restart had a higher frequency of experiencing side effects (44.2 versus 20.5 % of those willing; P < 0.001).ConclusionsFrom the osteoporosis patient's perspective, barriers to prescription treatment include a preference for alternative, non-prescription treatments and a fear of possible side effects. Side effects are one of the most common reasons for discontinuing osteoporosis medications, and they appear to be associated with a lack of willingness to restart treatment.

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Combination therapy for osteoporosis: a reappraisal.

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