No cases of incident drug-induced osteonecrosis
by Kristen Monaco, Contributing Writer, MedPage Today July 11, 2017
• Following moderate to high oral prednisolone use among older patients, alendronate (Fosamax) may be protective against fracture risk.
• Note that there were no reported cases of drug-induced osteonecrosis during the study, and alendronate usage was not linked to peptic ulcers among the study group.
Following moderate to high oral prednisolone use among older patients, alendronate (Fosamax) may be protective against fracture risk, a new study found.
In an adjusted model, oral alendronate use was associated with significantly lower risk of hip fractures (HR 0.35, 95% CI 0.22-0.54), reported Kristian F. Axelsson, MD, of Skaraborg Hospital in Skövde in Sweden, and colleagues.
In the study, there were hip fractures in patients receiving alendronate during a 1.32 year median follow-up (incidence rate 9.5, 95% CI 6.5-13.9 fractures per 1,000 person-years), compared with 73 hip fractures among the prednisolone-only group (IR 27.2, 95% CI 21.6-34.2 for an absolute rate difference of -17.6 (95% CI -24.8 to -10.4), they reported in JAMA.
“Alendronate is known to reduce the risk of vertebral fractures in patients taking prednisolone, but no studies were previously available regarding hip fracture, which is the most serious fracture, often leading to disability and increased risk of mortality,” co-author Mattias Lorentzon, MD, PhD, of Sahlgrenska University Hospital, in Mölndal, Sweden told MedPage Today.
“Since alendronate is now a generic compound (without patent) it is unlikely that there will be any large randomized trials, investigating the effect of alendronate on hip fracture risk in older patients taking prednisolone, in the future,” he added.
The authors collected participant information on adults, ages, 65 and older who were registered in Sweden’s Senior Alert database. A total of 1,802 individuals who were prescribed alendronate after a minimum of 3 months of 5 mg/d or higher of oral prednisolone were identified. They were then equally matched with individuals taking the same dosage of prednisolone without alendronate usage (n=3,604, 70% women). Individuals who were currently prescribed other treatments for osteoporosis, including risedronate, zoledronic acid, denosumab, testosterone, among others, were excluded from the analysis.
Findings were similar in an unadjusted Cox model, which reported alendronate treatment was still associated with a lowered hip fracture risk which was defined as a fractured femoral head, neck, trochanter, or subtrochanteric section of the femur (HR 0.35, 95% CI 0.23-0.55).
“Since previous studies have shown that several osteoporosis medications have the largest protective effect in the patients with the highest fracture risk, we were not surprised to see that alendronate was associated with a much lower hip fracture risk in the high-risk population we investigated — [elderly] patients using high doses of oral prednisolone,” Lorentzon explained.
Among secondary outcomes, alendronate treatment was also associated with reduced risk for major osteoporotic fracture in a multivariable Cox model (HR 0.53, 95% CI 0.38-0.73), any fracture (HR 0.58, 95% CI 0.46-0.73), and nonvertebral fracture (HR 0.55, 95% CI 0.43-0.71). Absolute risk reduction among these secondary outcomes for the alendronate group over a 30-month treatment period were as follows:
• Major osteoporotic fracture: 3.9% (95% CI 2.2-5.4%)
• Any fracture: 5.7% (95% CI 3.9-8.0%)
• Nonvertebral fracture: 5.5% (95% CI 3.6-7.5%)
The researchers noted these associated were only statistically significant among the postmenopausal female participants.
Axelsson’s group noted there were no reported cases of drug-induced osteonecrosis during the study. Alendronate usage was not linked to peptic ulcers among the study group: treatment versus no treatment: 10.9 (95% CI 7.7-15.5) versus 11.4 (95% CI 8.0-16.2) per 1,000 person-years (P=0.86). It also was not associated with an increased risk of mild upper gastrointestinal tract symptoms: 15.6 (95% CI 11.6-21.0) versus 12.9 (95% CI 9.3-18.0) per 1,000 person-years (P=0.40).
According to the American Association of Clinical Endocrinologists and the American College of Endocrinology’s clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis, the four approved agents — alendronate, risedronate, zoledronic acid (Zometa), and denosumab (Xgevia and Prolia) — are recommended as initial therapy for those at high risk for fracture. Oral agents, such as alendronate, are specifically recommended for patients with a lower or moderate fracture risk, including younger post-menopausal women without a prior history of fracture and moderately low T-Scores.
However, alendronate does not come without notable side effects, which have recently landed drug maker Merck in court for a “failure-to-warn” lawsuit specifically regarding the risk of thighbone fractures. In this analysis, there were only two reported incidents of femoral shaft fracture, one per study group.
For future studies,”we aim to continue to investigate osteoporosis medications and fracture outcomes in patients with other diseases and conditions, not studied in randomized trials before, using our national registers,” Lorentzon said.