New and Emerging Treatments for Osteoporosis
New and Emerging Treatments for Osteoporosis
Purpose of review: This review will focus on three new treatments for postmenopausal osteoporosis which have either been recently released (intravenous ibandronate), or have completed (zoledronic acid) or are currently in (denosumab) phase III trials.
Recent findings: A number of agents have demonstrated fracture risk reduction in randomized clinical trials, however, successful treatment of osteoporosis in the individual patient remains a challenge. Adherence to, and persistence with, all current osteoporosis medications are poor, being approximately 50% at 1 year for weekly bisphosphonates. Poor adherence to therapy makes it unlikely that the significant fracture reduction seen in clinical trials will be realized in clinical practice.
Summary: New therapies will not only have to demonstrate safety and efficacy, but also provide some advantage to patient persistence through either less frequent dosing schedules or elimination of gastrointestinal disturbances, the most common adverse effects encountered with bisphosphonates. This review will focus on three such agents that have either been recently released (intravenous ibandronate), or have completed (zoledronic acid) or are currently in (denosumab) phase III trials.
Currently approved therapies for the prevention or treatment of osteoporosis include the selective receptor modulator raloxifene, and the bisphosphonates alendronate, risedronate and ibandronate. In the USA, calcitonin nasal spray and teriparatide are approved for treatment and estrogen therapy is approved for the management of postmenopausal symptoms, but no longer approved for the treatment of osteoporosis. The bisphosphonates are considered the drugs of choice based upon their demonstrated efficacy in reducing vertebral and nonvertebral fracture risk.
As with other chronic asymptomatic disorders, long-term adherence and persistence with current osteoporosis medications are poor. Factors associated with nonadherence are multiple and include poor health literacy, fear of adverse effects, medication costs, polypharmacy and complex dosing regimens. Osteoporosis patients who are not fully adherent to their medication have smaller increases in bone mineral density and a significantly greater numbers of fractures compared with adherent patients. A recent study examined the relationship of medication compliance to fracture risk from 35 537 women in two US claims databases over a 2-year period. During a 24-month period, only 43% were refill compliant (medication possession ratio ≥ 0.80) and 20% were persistent (no gap in refills for over 30 days during 24 months) with bisphosphonate therapy. There was a significant relationship between refill compliance and fracture risk reduction, starting at refill compliance rates of approximately 50% and becoming stronger at compliance rates of 75% and higher. This study highlights both the poor state of current compliance with osteoporosis medications and the potential for optimal fracture reduction only at high levels of compliance, not currently achieved with once weekly bisphosphonates in clinical practice.
The rest of this paper will focus on recent evidence supporting the use of less frequent dosing regimens with intravenous ibandronate every 3 months, and with two agents not yet approved by the Food and Drug Administration, once-yearly zoledronic acid and twice-yearly denosumab.
Purpose of review: This review will focus on three new treatments for postmenopausal osteoporosis which have either been recently released (intravenous ibandronate), or have completed (zoledronic acid) or are currently in (denosumab) phase III trials.
Recent findings: A number of agents have demonstrated fracture risk reduction in randomized clinical trials, however, successful treatment of osteoporosis in the individual patient remains a challenge. Adherence to, and persistence with, all current osteoporosis medications are poor, being approximately 50% at 1 year for weekly bisphosphonates. Poor adherence to therapy makes it unlikely that the significant fracture reduction seen in clinical trials will be realized in clinical practice.
Summary: New therapies will not only have to demonstrate safety and efficacy, but also provide some advantage to patient persistence through either less frequent dosing schedules or elimination of gastrointestinal disturbances, the most common adverse effects encountered with bisphosphonates. This review will focus on three such agents that have either been recently released (intravenous ibandronate), or have completed (zoledronic acid) or are currently in (denosumab) phase III trials.
Currently approved therapies for the prevention or treatment of osteoporosis include the selective receptor modulator raloxifene, and the bisphosphonates alendronate, risedronate and ibandronate. In the USA, calcitonin nasal spray and teriparatide are approved for treatment and estrogen therapy is approved for the management of postmenopausal symptoms, but no longer approved for the treatment of osteoporosis. The bisphosphonates are considered the drugs of choice based upon their demonstrated efficacy in reducing vertebral and nonvertebral fracture risk.
As with other chronic asymptomatic disorders, long-term adherence and persistence with current osteoporosis medications are poor. Factors associated with nonadherence are multiple and include poor health literacy, fear of adverse effects, medication costs, polypharmacy and complex dosing regimens. Osteoporosis patients who are not fully adherent to their medication have smaller increases in bone mineral density and a significantly greater numbers of fractures compared with adherent patients. A recent study examined the relationship of medication compliance to fracture risk from 35 537 women in two US claims databases over a 2-year period. During a 24-month period, only 43% were refill compliant (medication possession ratio ≥ 0.80) and 20% were persistent (no gap in refills for over 30 days during 24 months) with bisphosphonate therapy. There was a significant relationship between refill compliance and fracture risk reduction, starting at refill compliance rates of approximately 50% and becoming stronger at compliance rates of 75% and higher. This study highlights both the poor state of current compliance with osteoporosis medications and the potential for optimal fracture reduction only at high levels of compliance, not currently achieved with once weekly bisphosphonates in clinical practice.
The rest of this paper will focus on recent evidence supporting the use of less frequent dosing regimens with intravenous ibandronate every 3 months, and with two agents not yet approved by the Food and Drug Administration, once-yearly zoledronic acid and twice-yearly denosumab.
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