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Clinical Review State of the Art Review

Bisphosphonates for the prevention and treatment of osteoporosis

BMJ 2015; 351 doi: (Published 02 September 2015) Cite this as: BMJ 2015;351:h3783
Treating osteoporosis with bisphophonates infographic
Click here to see an interactive graphic, showing patient assessment, treatment pathways and decisions at each stage.

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Author's Reply

We appreciate the pertinent questions raised by Dr. Sharvill. While seeking to be concise yet anticipating an interest in a broader discussion of bisphosphonate use in special populations, we chose to reference articles we deemed of interest to the reader seeking further information. Regarding bisphosphonate trials involving patients receiving glucocorticoid therapy, Rizzoli and Biver note a consistent effect on preventing loss of bone mineral density or increasing bone mineral density with alendronate, risedronate and zoledronic acid.1 In some, but not all, trials alendronate and risedronate reduced the risk of vertebral fractures. This review also summarizes several regional and professional society guidelines for the management of bone health in patients receiving glucocorticoid therapy which variably integrate glucocorticoid dose, duration, bone mineral density and/or fracture risk in decision-making.

Whether bisphosphonates reduce the risk of osteoporotic fracture in those without osteoporosis (absent fracture and femur neck T-score > -2.5) is of considerable debate. We sought to convey the uncertainty regarding the presence or magnitude of benefit of bisphosphonates in such patients in general and in those for who the incorporation of clinical risk factors (e.g., FRAX) might suggest a benefit. Based on our review and interpretation, the best available evidence favors the use of bisphosphonate in those with densitometric osteoporosis (i.e., femur neck T-score < -2.5) or established osteoporosis (i.e., vertebral fracture, hip fracture).

Dr. Sharvill points out that patients and clinician routinely encounter questions surrounding the intersection of bisphosphonates and calcium and/or vitamin D nutrition. The recent analyses and interpretations thereof have focused on calcium and/or vitamin D and bone mineral density or fractures independent of bisphosphonate therapy. Trials of bisphosphonate therapy independent of an accounting of or intervention regarding calcium and vitamin D nutrition are few. Still, our primary purpose in including mention of calcium and vitamin D was to draw attention to patients who may be overtly calcium and/or vitamin D malnourished. These patients may have an element of or overt osteomalacia contributing to low bone mineral density. They are at risk for hypocalcemia with bisphosphonate therapy. Most important, they are initially best treated with correction of their calcium and vitamin D nutrition and identification of the factors leading to such. Doing so may resolve their metabolic bone disease and obviate the need for any pharmacotherapy.

1. Rizzoli R. Biver E. Glucocorticoid-induced osteoporosis: who to treat with what agent? Nat Rev Rheumatol 2015;11:98-109.

Competing interests: No competing interests

23 October 2015
Kurt A. Kennel
Consulting Endocrinologist
Spyridoula Maraka
Mayo Clinic
Rochester, MN, USA