Depot medroxyprogesterone acetate (DMPA)-associated early-onset osteoporotic fracture.

Summary: Depot medroxyprogesterone acetate (DMPA) is a highly effective injectable contraceptive, but is associated with reduced bone mineral density (BMD) and increased fracture risk in some studies because it inhibits the hypothalamic-pituitary-ovarian axis. Herein, we present the diagnostic challenging case of a premenopausal woman with an unusual hip fracture and prolonged use of intramuscular DMPA injection. Whole-exome sequencing revealed a rare heterozygous variant of the ALPL gene, which could cause adult-onset hypophosphatasia (HPP). However, it was classified as a variant of unknown significance. Our case highlights the fracture risk from long-term use of DMPA, which is widely used as progestogen-only contraceptive method in low- and middle-income countries. Clinicians should inform women on the potential adverse effect of prolonged use of DMPA for contraception on bone health and advise them to adopt healthy lifestyle habits, with adequate calcium and vitamin D intake. Learning points: Evidence shows that intramuscular depot medroxyprogesterone acetate (DMPA) negatively affects BMD by inhibiting the hypothalamic-pituitary-ovarian axis. However, the risk of bone fragility fracture from DMPA remains uncertain because of paucity of data on fracture incidence. Herein, we present a case of a premenopausal woman with an unusual hip fracture and a history of prolonged use of intramuscular DMPA contraception. Our case also highlights that the patient's clinical presentation is essential for interpreting genetic sequencing results.