“We are hopeful that in the future we can determine which patients are more likely to suffer them,” they added.
Another safety concern with bisphosphonate therapy has been osteonecrosis of the jaw. Current estimates of the incidence of osteonecrosis of the jaw range from about 1/10,000 to 1/100,000 patient treatment-years. Factors that can potentially increase this risk for patients treated with bisphosphonates include poor oral hygiene, smoking, diabetes, concomitant glucocorticoids and/or chemotherapy use, and invasive dental procedures. The report says that there appears to be a trend for increased risk of osteonecrosis of the jaw with duration of bisphosphonate use, but the quality of the evidence for such an association is poor. The task force recommends that risk factors for osteonecrosis of the jaw be included in the periodic assessment of benefits and risk of bisphosphonate therapy.
“For most patients treated for osteoporosis, the bisphosphonate-associated benefit of reduced fracture risk beyond five years, albeit with evidence for vertebral fracture only, is greater than the risk of developing either osteonecrosis of the jaw or an atypical femoral fracture,” the report states.
Dr. Bolster says the risks and benefits of bisphosphonate therapy should always be considered, with the risk of therapy at the initiation of treatment different from the risks to consider after three to five years of treatment. “Fracture risk reduction is the tremendous benefit attained with initiation of treatment, and this is weighed against the potential risk of therapy, including gastrointestinal effects, flu-like symptoms, bone pain.”
A patient’s risk should be reassessed after five years of oral bisphosphonate therapy or three years of intravenous (IV) zoledronic acid therapy.
Risk stratification is warranted at the time more prolonged therapy is being considered, she says, with a consideration of the patient’s hip T-score, prior history of hip or spine fracture, fracture while on therapy (e.g., hip, spine, humerus, forearm), age, medication use (such as aromatase inhibitors, glucocorticoids) or a new diagnosis of a condition associated with a secondary cause of bone loss.
Drs. Adler and El-Hajj Fuleihan note that risk stratification is based on DXA scans and various calculators, such as FRAX (Fracture Risk Assessment Tool), that incorporate clinical factors, such as age and personal history of fractures. It’s also important to have the patient on adequate dietary calcium, keep their 25-hydroxyvitamin D level of at least 30 ng/mL, maintain muscle strength, avoid falls, improve home safety and take medications correctly and regularly, they say.
Other Populations
The report additionally considers what is known about use of long-term bisphosphonate therapy in patients taking continuous oral glucocorticoids. Spine fractures occur with greater frequency in older patients on higher doses of glucocorticoids, regardless of their bone mineral density. The report suggests that for women who require continued bone-protective therapy and who have received bisphosphonates for more than five years, switching to teriparatide may be considered. Men older than age 50 who are treated with long-term glucocorticoids greater than 5 mg/d are also at increased risk of fracture and may benefit from continuation of bisphosphonate therapy.
