Summary of AHRQ's comparative effectiveness review of treatment to prevent fractures in men and women with low bone density or osteoporosis: update of the 2007 report.

BACKGROUND

In 2007, the Agency for Healthcare Research and Quality(AHRQ) published a systematic review on the comparative effectiveness of treatments for osteoporosis. The review included studies on the benefits and risks of medications and therapies used to prevent fractures in postmenopausal women and men with low bone density (osteopenia) or osteoporosis. Factors that may affect adherence to treatment, and monitoring for the identification of those most likely to benefit from treatment were also included in this review. AHRQ published an updated review in March 2012 that summarized the benefits and risks of osteoporosis medications in treatment and prevention of osteoporosis, including bisphosphonates (aledronate, risedronate, ibandronate, zoledronic acid), parathyroid hormone, teriparatide, calcitonin, estrogens (for prevention in postmenopausal women), selective estrogen receptor modulators (raloxifene), and denosumab(approved by the FDA in 2010). In addition, dietary and supplemental calcium and vitamin D, as well as weight-bearing exercise, for the preservation of bone mass and the decrease of fracture risk in patients with osteoporosis, were evaluated.

OBJECTIVES

To (a) familiarize health care professionals with the methods and findings from AHRQ's 2012 comparative effectiveness review on treatments to prevent fractures in men and women with low bone density or osteoporosis, (b) encourage consideration and application of the findings of this review in clinical and managed care settings, and (c) identify limitations and gaps in the existing research with respect to the benefits and risks of treatments for osteoporosis.

SUMMARY

Osteoporosis is a prevalent systemic skeletal disease caused by bone deterioration and loss of mass resulting in fractures, chronic pain and physical disability. It is common in postmenopausal women but men are at risk as well for fractures associated with low bone density. The increasing prevalence and cost of treating osteoporosis make the study of safety and effectiveness for currently available osteoporosis therapies pertinent and timely. In 2012, the Agency for Healthcare Research and Quality (AHRQ) published an updated review on the effectiveness and safety of treatments for osteoporosis, including new therapies for the prevention of vertebral and nonvertebral fractures in postmenopausal women and men.The interventions assessed in the review included 1 biological agent, pharmacological agents, dietary and supplemental calcium and vitamin D, and weight-bearing exercise. The updated report included the new agents and indications approved after the 2007 report and new data on effectiveness and adverse events associated with the bisphosponates; calcitonin was determined by the reviewers to not be appropriate therapy for osteoporosis and was excluded. The updated review examined 5 key questions focused on comparative review of all FDA-approved medicines for osteoporosis in fracture risk reduction, effectiveness in racial/ethnic subpopulations as well as different risk stratification using FRAX (World Health Organization Fracture Risk Assessment Tool) or other cutoffs, compliance and adherence, adverse effects of medications, the prediction of treatment efficacy using bone mineral density (BMD) monitoring by dual energy x-ray absorptiometry (DXA), and comparative effectiveness of long-term therapy.The AHRQ reviewers found high strength of evidence to support a reduction in risk of vertebral, nonvertebral and hip fractures in postmenopausal women with osteoporosis treated with 1 of 4 agents (alendronate, risedronate, zoledronic acid, or denosumab). A risk reduction for vertebral fractures in postmenopausal women with osteoporosis treated with ibandronate, teriparatide, or raloxifene therapy was supported with high-strength evidence. Evidence was graded high strength for reduction of vertebral and hip fracture with estrogen therapy in postmenopausal women but not in women with established osteoporosis. Evidence was graded moderate for a reduction in nonvertebral fractures with teriparatide or calcium monotherapy. Moderate or low-moderate strength of evidence showed that calcium alone does not reduce the risk of vertebral or nonvertebral fracture, and that vitamin D has mixed results on decreasing overall fracture risk. High-strength evidence supports a reduction in the risk of hip fracture with calcium treatment. Vitamin D treatment significantly reduced vertebral fractures among patients with primary osteoporosis. The combination of calcium plus vitamin C did not reduce vertebral fracture risk, but did reduce nonvertebral fracture risk in certain populations. Calcium plus vitamin D did decrease the risk of fracture in elderly women but not in elderly men. Adherence and persistence to osteoporosis medications varied depending on patient age, prior history of fracture, dosing frequency, concomitant use of other medications, and adverse effects. Adherence to treatment improved with weekly dosing compared with daily regimens, but evidence was lacking to show monthly regimens improved adherence over weekly regimens. This article recaps the key findings from the AHRQ 2012 review for the purpose of informing health care providers about the efficacy and safety of therapies used to prevent osteoporotic vertebral, nonvertebral, hip, and wrist fractures. Scientific literature on the effects of risk factors, adherence, BMD monitoring, and long-term therapy on patient outcomes is reviewed in order to inform prescribing decisions. In addition, applications of the AHRQ findings to practice are discussed to provide clinicians with information needed to provide evidence-based care for their patients.