Hormones

Osteoporosis Is Multiple Diseases — and Treatment Should Match the Subtype

Osteoporosis is not one disease but a collection of overlapping syndromes with different underlying drivers — postmenopausal estrogen loss, age-related bone decline, eating disorders, and weight loss from GLP-1 drugs each erode bone through distinct mechanisms. This review synthesizes new mechanistic understanding, including the underappreciated role of bone marrow fat (BMAT) in shaping the marrow environment, the skeletal risks of various forms of weight loss, and the bidirectional effects of parathyroid hormone depending on how it is administered. Exercise protects bone via mechanical loading, myokines, autophagy, and epigenetic changes, but benefits vary by exercise type. The authors argue that PTH analogs, sclerostin antibodies, and targeted exercise prescriptions should be matched to each patient's specific osteoporosis subtype rather than applied uniformly.