Disuse osteoporosis may be focal, involving a single bone or limb (arthritis or limb immobilization), or it may be generalized (prolonged bed rest or paralysis). With generalized immobilization, bone loss is most profound and rapid in the trabecular bone tissues of the axial skeleton and weight-bearing appendicular long bones.

Nevertheless, even with prolonged immobilization, loss of bone mass does not continue indefinitely. Results of studies carried out on dogs show that tubular bones exhibited temporal and envelope-specific patterns of change in bone mass after long-term immobilization in a cast. In these studies, a rapid initial loss of bone occurred over the first 6 weeks of immobilization. By the 12th week of immobilization, a rebound in bone mass occurred, although these levels were still below those before immobilization. Thereafter, a slower, longer-lasting bone loss continued and ended at 32 weeks of immobilization, with bone mass levels reaching a plateau at approximately 50% of original values.

In the short first phase, bone loss involved the periosteal, osteonal (haversian), and corticoendosteal envelopes. In the later, sustained-loss phase, the periosteal envelope was affected, resulting in a smaller bone with a slightly widened medullary canal and a thinner, more porous cortex. This latter trend was noted more so in relatively younger dogs (less so in older dogs) and may be in part attributed to a suppression of residual cortical bone growth in girth by immobilization of the younger dogs. Also, a similar suppression of cortical bone growth at mid-diaphysis has been reported for young rats flown in space experiencing weeks of weightlessness and mechanical disuse.