Osteopenia in the immobilized rat hind limb is associated with increased bone resorption and decreased bone formation.
The lack of mechanical function (disuse) caused by paralysis, immobilization or weightlessness, leads to osteopenia. This study examines the contribution of bone resorption and bone formation to osteopenia of disuse, during six weeks of limb-immobilization in the growing rat. Male Sprague-Dawley rats of approximately 200 g underwent unilateral hind-limb immobilization by either tenotomy at the knee joint or sciatic neurectomy, while control rats were sham-operated. Animals were sacrificed at 30 and 72 hours, 10, 26 and 42 d postsurgery. Femora were ashed to determine the total mineral content and histomorphometric parameters, static and dynamic, were measured in the secondary spongiosa of the proximal tibial metaphysis. No difference was found in the femoral length of the immobilized legs. Bone loss in the immobilized leg versus the nonimmobilized one, at 10, 26 and 42 d post-surgery was 18.0, 14.0 and 11.2% of femoral mineral content in the tenotomy group, respectively, and 12.4, 16.1 and 15.7% in the neurectomy group. Loss of metaphyseal trabecular bone volume at 10, 26 and 42 days amounted to 67.8, 49.3 and 52.9% in the tenotomy group, respectively, and 70.5, 59.0 and 72.9% in the neurectomy group. The bone loss was caused by: (a) A rapid surge in bone resorption, reflected in a significant increase in the number of osteoclasts per mm bone surface at 30 and 72 h and in the osteoclast surface at 72 h but not at later times, and (b) a sustained decrease in bone mineral apposition rate and bone formation rate (osteoblast-referent) throughout the 42-day immobilization period suggesting osteoblastic hypofunction (reduced activity).(ABSTRACT TRUNCATED AT 250 WORDS)
Weinreb
M
M
Department of Bone Biology and Osteoporosis Research, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486.
Rodan
G A
GA
Thompson
D D
DD
D000818:Animals; D015519:Bone Density; D001846:Bone Development; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism; D006614:Hindlimb; D007103:Immobilization; D008297:Male; D010010:Osteoclasts / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors