The mechanisms of bone loss may involve the following: Local changes in cytokine production, particularly involving cytokines such as receptor activator of nuclear factor kappa-B ligand [RANKL] that increase bone resorption by promoting differentiation and maturation of osteoclasts Impaired formation response during bone remodeling, probably caused by age-related decline in the number and activity of osteoblasts, partly related to cytokine-mediated increases in the protein sclerostin Other factors that affect bone resorption such as parathyroid hormone (PTH) and vitamin D Idiopathic osteoporosis refers to the rare cases of fragility fractures in children, adolescents, premenopausal women, or men < 50 years with normal gonadal function and no detectable secondary cause, including in those with low bone mass (low Z-scores on dual-energy x-ray absorptiometry [DXA] scans).