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.