{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:13:28Z","timestamp":1787022808553,"version":"build-2736575974"},"reference-count":9,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"\n Summary<\/jats:title>\n \n 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\u2013pituitary\u2013ovarian 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\n ALPL<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>\n \n Learning points<\/jats:title>\n \n \n Evidence shows that intramuscular depot medroxyprogesterone acetate (DMPA) negatively affects BMD by inhibiting the hypothalamic\u2013pituitary\u2013ovarian axis.<\/jats:p>\n <\/jats:list-item>\n \n However, the risk of bone fragility fracture from DMPA remains uncertain because of paucity of data on fracture incidence.<\/jats:p>\n <\/jats:list-item>\n \n Herein, we present a case of a premenopausal woman with an unusual hip fracture and a history of prolonged use of intramuscular DMPA contraception.<\/jats:p>\n <\/jats:list-item>\n \n Our case also highlights that the patient\u2019s clinical presentation is essential for interpreting genetic sequencing results.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-24-0123","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T11:51:07Z","timestamp":1747309867000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":2,"title":["Depot medroxyprogesterone acetate (DMPA)-associated early-onset osteoporotic fracture"],"prefix":"10.1530","volume":"2025","author":[{"given":"Yotsapon","family":"Thewjitcharoen","sequence":"first","affiliation":[{"name":"Theptarin Diabetes, Thyroid, and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veekij","family":"Veerasomboonsin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Vimut-Theptarin Hospital, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soontaree","family":"Nakasatien","sequence":"additional","affiliation":[{"name":"Theptarin Diabetes, Thyroid, and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thep","family":"Himathongkam","sequence":"additional","affiliation":[{"name":"Theptarin Diabetes, Thyroid, and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Contraception","first-page":"577","article-title":"Bone mineral density and depot medroxyprogesterone acetate","volume":"73","author":"Albertazzi P","year":"2006","unstructured":"Albertazzi P\n, \nBottazzi M\n & \nSteel SA\n\n. Bone mineral density and depot medroxyprogesterone acetate. Contraception 2006 73 577\u2013583. (https:\/\/doi.org\/10.1016\/j.contraception.2006.02.004)"},{"key":"bib2","series-title":"Fertil Steril","first-page":"1466","article-title":"Bone mineral density loss and recovery during 48 months in first-time users of depot medroxyprogesterone acetate","volume":"86","author":"Clark MK","year":"2006","unstructured":"Clark MK\n, \nSowers M\n, \nLevy B\n, et al.\n Bone mineral density loss and recovery during 48 months in first-time users of depot medroxyprogesterone acetate. Fertil Steril 2006 86 1466\u20131474. (https:\/\/doi.org\/10.1016\/j.fertnstert.2006.05.024)"},{"key":"bib3","series-title":"J Adolesc Health","first-page":"296","article-title":"Depot medroxyprogesterone acetate and bone mineral density in adolescents\u2013the Black Box Warning: a position paper of the society for adolescent medicine","volume":"39","author":"Cromer BA","year":"2006","unstructured":"Cromer BA\n, \nScholes D\n, \nBerenson A\n, et al.\n Depot medroxyprogesterone acetate and bone mineral density in adolescents\u2013the Black Box Warning: a position paper of the society for adolescent medicine. J Adolesc Health 2006 39 296\u2013301. (https:\/\/doi.org\/10.1016\/j.jadohealth.2006.03.011)"},{"key":"bib4","series-title":"Obstet Gynecol","first-page":"1398","article-title":"Committee Opinion No. 602: Depot medroxyprogesterone acetate and bone effects","volume":"123","year":"2014","unstructured":"Committee Opinion No. 602: Depot medroxyprogesterone acetate and bone effects. Obstet Gynecol 2014 123 1398\u20131402. (https:\/\/doi.org\/10.1097\/01.AOG.0000450758.95422.c8)"},{"key":"bib5","series-title":"Genet Med","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards S","year":"2015","unstructured":"Richards S\n, \nAziz N\n, \nBale S\n, et al.\n Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 17 405\u2013424. (https:\/\/doi.org\/10.1038\/gim.2015.30)"},{"key":"bib6","series-title":"Steroids","first-page":"11","article-title":"Estrogen and bone health in men and women","volume":"99","author":"Cauley JA","year":"2015","unstructured":"Cauley JA\n\n. Estrogen and bone health in men and women. Steroids 2015 99 11\u201315. (https:\/\/doi.org\/10.1016\/j.steroids.2014.12.010)"},{"key":"bib7","series-title":"Fertil Steril","first-page":"697","article-title":"Depot medroxyprogesterone acetate use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density","volume":"93","author":"Walsh JS","year":"2010","unstructured":"Walsh JS\n, \nEastell R\n & \nPeel NF\n\n. Depot medroxyprogesterone acetate use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density. Fertil Steril 2010 93 697\u2013701. (https:\/\/doi.org\/10.1016\/j.fertnstert.2008.10.004)"},{"key":"bib8","series-title":"Osteoporos Int","first-page":"291","article-title":"The impact of depot medroxyprogesterone acetate on fracture risk: a case-control study from the UK","volume":"28","author":"Kyvernitakis I","year":"2017","unstructured":"Kyvernitakis I\n, \nKostev K\n, \nNassour T\n, et al.\n The impact of depot medroxyprogesterone acetate on fracture risk: a case-control study from the UK. Osteoporos Int 2017 28 291\u2013297. (https:\/\/doi.org\/10.1007\/s00198-016-3714-4)"},{"key":"bib9","series-title":"J Clin Densitom","first-page":"340","article-title":"Hypophosphatasia in adults: clinical spectrum and its association with genetics and metabolic substrates","volume":"23","author":"Lefever E","year":"2020","unstructured":"Lefever E\n, \nWitters P\n, \nGielen E\n, et al.\n Hypophosphatasia in adults: clinical spectrum and its association with genetics and metabolic substrates. J Clin Densitom 2020 23 340\u2013348. 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