Efficacy

Drugs that have proved effective in preventing fractures in women with PMO. Antiresorptive drugs reduced rates of vertebral fractures by 30% to 70%, and teriparatide reduced these rates by 65% to 69%. Efficacy of treatment in preventing fractures was seen relatively early, typically within 12 to 18 months. However, several extension trials suggest that the preventive effect plateaus over time, with no difference in fracture rates observed between antiresorptive treatment and placebo arms after four to six years of therapy. In addition, efficacy was most pronounced in women at greater risk (lower baseline T-scores, older age, fracture history).

Differences in efficacy between the major classes of agents may be related to differences in their mechanisms of action. However, compliance with medication may also account for some of the difference in efficacy between antiresorptives and teriparatide. Cramer and Gold reported that one-year compliance with oral bisphosphonates was generally low (17% to 78%). Although once-yearly zoledronic acid (Reclast) is not approved for use in PMO, it helps solve the problem of poor compliance with bisphosphonate regimens and might explain the higher fracture efficacy rates seen with zoledronic acid compared with other bisphosphonates. However, the incidence of serious atrial fibrillation observed with zoledronic acid in the HORIZON trial warrants further evaluation. Apcalis Oral Jelly

Although teriparatide possesses greater efficacy in fracture prevention than other approved antiresorptive agents, several problems are related to its use. First, because of the potential risk for osteosarcoma, teriparatide should not be used for more than two years. However, two years of therapy might not be sufficient for the long-term prevention of fractures. Evidence is emerging that there is benefit to augmenting teriparatide therapy with an antiresorptive agent to maintain bone mass and structural gains over time. However, identifying the most effective combination is important to minimize the risk of the anti-resorptive agent’s blunting the bone anabolic properties of teri-paratide by reducing the rate of bone turnover.

Several trials have studied the effects of combining PTH with a bisphosphonate on bone formation. Findings have suggested that using PTH prior to a bisphosphonate may ensure that the full effects of PTH are realized, although using PTH following a course of alendronate therapy is also beneficial.

There is no evidence of additional benefit in using PTH and a bisphosphonate concomitantly. The combination of an antiresorptive and an anabolic agent remains to be fully addressed in clinical trials, and studies with fracture endpoints are warranted to measure the impact of combination treatment on clinical outcomes.
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Economics of Fracture Prevention

Besides efficacy, the economics of preventing fractures in patients with PMO should be a primary consideration in determining which patients to treat and which drug class to use. At a cost of $763 to $894 per year, antiresorptive agents are cost-effective, compared with placebo, when they are used to treat osteoporosis as diagnosed by prior fragility fractures or T-scores below -2.5 plus another risk factor, such as advancing age.

Antiresorptive therapy for preventing fractures in women with T-scores above -2.5 without a prior fracture or another risk factor is not cost-effective. However, many fractures occur in women with T-scores above -2.5; thus, the cost-effectiveness of fracture prevention in lower-risk populations should be re-evaluated when generic antiresorptive agents become avail-able.

At an annual cost of approximately $6,700, limited data suggest that teriparatide is not cost-effective for PMO when used alone. Teriparatide plus alendronate was cost-effective only in the highest-risk women 70 years of age and older with T-scores below -4.0. Even at a higher price, teriparatide has a cost-effective place in the treatment of PMO for those at greatest risk for fracture.

Overall, pharmacoeconomic data for PMO agents are incomplete. Data for antiresorptive agents are largely focused on alendronate; only one published study of teriparatide has been identified. Furthermore, the studies generally rely on BMD measures plus other risk factors such as age and prior fracture as the indicators of risk. As recognized by the WHO, however, BMD measures are not always available or feasible. Thus, cost-effectiveness studies in patients with various combinations of non-BMD risk factors would be useful for clinicians and managed care plans in selecting cost-effective care for broad populations or individual s when BMD data are not available.

Promising products under review for use in the U.S. include strontium ranelate and PTH (1-84). Early trials for these agents have shown a reduced risk of fractures. If they are approved for use in the U.S., pharmacoeconomic evaluations will be warranted to help define a cost-effective role in PMO fracture prevention.

CONCLUSION

Pharmacotherapy is a cost-effective approach to preventing fractures in women with PMO. Antiresorptive drugs are a mainstay of treatment; they are cost-effective in preventing fractures in PMO populations at risk for fractures because of their history of prior fractures, low T-scores, and advancing age.

Teriparatide, the only available bone anabolic agent, has greater efficacy in fracture prevention than the approved anti-resorptive agents. Because of the cost of treatment, however, it appears to be cost-effective only when it is combined with an antiresorptive drug and when its use is reserved for very-high-risk populations with multiple risk factors, including advancing age and very low T-scores.
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Both PTH (1-84) and strontium ranelate, which is available outside the U.S., have demonstrated efficacy in preventing fractures in postmenopausal women. Thus, these agents have the potential to enhance therapeutic options. Future pharmaco-economic studies for these new agents are warranted to identify their cost-effectiveness.