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Use of oral bisphosphonates and risk of osteonecrosis of the jaw: large prospective cohort study in UK women

Wotton CJ, Green J, Brown A, Armstrong ME, Floud S, Beral V, Reeves GK for the Million Women Study collaborators

Bone 2019 124:69-74.

About 1 in 10 postmenopausal UK women are currently prescribed oral bisphosphonates, but there are concerns about their adverse effects. Osteonecrosis of the jaw is a recognised uncommon but important side effect of intravenous bisphosphonates, but epidemiological evidence on risk of osteonecrosis of the jaw associated with oral bisphosphonate use is less conclusive. The incidence of hospital admission with osteonecrosis of the jaw was examined among 521,695 Million Women Study participants, aged 64.7 years at baseline. Cox proportional hazards regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) associated with use of oral bisphosphonates in postmenopausal women followed-up by record-linkage to National Health Service hospital admission databases. During mean follow-up of 8.2 years per woman, 100 women were admitted to hospital with first recorded osteonecrosis of the jaw, at mean age 72.4 years. Almost a third (29/100) of the cases had ever-used oral bisphosphonates. Ever-users had a six-fold increased risk of hospital admission for osteonecrosis of the jaw, when compared with never-users (adjusted RR = 6.09, 95% CI 3.83-9.66; p < 0.0001). The relative risk for osteonecrosis of the jaw in never-users of oral bisphosphonates was increased in women with prior cancer (RR = 3.40, 2.22-5.22, p < 0.0001). The estimated absolute risk of hospital admission for osteonecrosis of the jaw over a 5-year period from age 70 to 74 in women without prior cancer was 0.09 per 1000 in never-users and 0.69 per 1000 in ever-users of oral bisphosphonates. In this UK population of postmenopausal women, use of oral bisphosphonates was associated with a 6-fold increased risk of hospital admission with osteonecrosis of the jaw, accounting for around one-third of cases, with an excess risk of about 0.6/1000 users over 5 years.