THE EFFECTS OF 12 WEEKS OF BED REST ON BONE-HISTOLOGY, BIOCHEMICAL MARKERS OF BONE TURNOVER, AND CALCIUM HOMEOSTASIS IN 11 NORMAL SUBJECTS

This study was undertaken to examine the effects of 12 weeks of skelet al unloading on parameters of calcium homeostasis, calcitropic hormone s, bone histology, and biochemical markers of bone turnover in 11 norm al subjects (9 men, 2 women; 34 +/- 11 years of age). Following an amb ulatory control evaluation, all subjects underwent 12 weeks of bed res t. An additional metabolic evaluation was performed after 12 days of r eambulation. Bone mineral density declined at the spine (-2.9%, p = 0. 092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest pr ompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinar y calcium increased from a pre-bed rest value of 5.3 mmol/day to value s as high as 7.3 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly durin g bed rest, although the mean values remained within normal limits. Si gnificant changes in bone histology included a suppression of osteobla stic surface for cancellous bone (3.1 +/- 1.3% to 1,9 +/- 1.5%, p = 0. 0142) and increased bone resorption for both cancellous and cortical b one. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4. 0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 8.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/ - 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic sur face doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemi cal markers of bone formation (osteocalcin, bone-specific alkaline pho sphatase, and type I procollagen extension peptide) did not change sig nificantly during bed rest. Urinary biochemical markers of bone resorp tion (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I c ollagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under th e conditions of this study, the human skeleton appears to respond to u nloading by a rapid Land sustained increase in bone resorption and a m ore subtle decrease in bone formation.