Balancing risks and benefits of bisphosphonates
Bisphosphonate is one of the first-line therapy for treating osteoporosis, but its long-term use should take into account the balance between its antifracture benefit and risk of adverse events such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ), according to a presentation at the AFOS 2017 Meeting in Kuala Lumpur, Malaysia.
Citing a 10-year study on the bisphosphonate alendronate in postmenopausal women with osteoporosis, the antifracture efficacy of alendronate 10 mg daily was sustained with continuous increase in lumbar spine bone mineral density (BMD) over the years (13.7 percent increase vs baseline; p<0.001), observed Dr Atsushi Suzuki of Fujita Health University in Toyoake, Japan. [AFOS 2017, abstract SA5.2; N Engl J Med 2004;350:1189-1199]
Also being highlighted were the HORIZON-PFT* and HORIZON-RFT** studies, which showed that the cumulative risk of hip fracture and mortality at 3 years was lower with zoledronic acid vs placebo. [J Clin Endocrinol Metab 2013;98:557-563]
“Clearly, bisphosphonate is one of the first-line medicine to prevent osteoporotic fractures,” said Suzuki.
However, long-term bisphosphonate use has been associated with major side effects including ONJ, AFF, and upper gastrointestinal tract symptoms such as abdominal discomfort, diarrhoea, and vomiting.
ONJ occurred most commonly in cancer patients in whom high doses of bisphosphonates are used at frequent intervals. [J Bone Miner Res 2015;30:3-23] Nonetheless, other medications such as denosumab and anticancer agents have also been associated with ONJ, noted Suzuki.
“The high risk for ONJ with zoledronate and denosumab was mainly observed in those who were treated for prevention of skeletal-related events, whereas there was limited evidence for such risk in those who were treated for osteoporosis,” he said.
In addition, ONJ also occurred in the general population at an incidence rate of 1/100,000 person/year compared with 1.04-69/100,000 person/year in osteoporosis patient population on bisphosphonates. Other risk factors for developing ONJ include invasive dental treatment, poor oral hygiene, ill-fitting dentures, and use of glucocorticoids or other drugs such as antiangiogenic agents. [J Bone Miner Res 2015;30:3-23]
“Therefore, ONJ is not specific for bisphosphonates, and such rare events are outweighed by fracture risk reduction by bisphosphonates especially in high fracture-risk patients,” said Suzuki.
According to the latest position paper on ONJ, drug holiday before tooth extraction was no longer supported for preventing ONJ, Suzuki observed, adding that maintenance of good oral hygiene is an important preventive strategy. [J Bone Miner Metab 2017;35:6-19]
In terms of AFF, the risk of AFF increased with the duration of bisphosphonate treatment and the risk of fracture decreased rapidly after stopping bisphosphonates. [J Bone Miner Metab 2015;33:311-318]
“Asians have a higher risk of AFF than Caucasians. Comorbidities such as diabetes and chronic kidney disease [also] contribute to an increased risk of AFF,” said Suzuki, suggesting that a 2–3 years drug holiday can be considered in women with low fracture risk after 3–5 years of bisphosphonate treatment. [J Bone Miner Res 2016;31:16-35]