A noninvasive analysis of urinary musculoskeletal collagen metabolism markers from rhesus monkeys subject to chronic hypergravity

Abstract

Martinez DA, Patterson-Buckendahl PE, Lust A, Shea-Rangel KM, Hoban-Higgins TM, Fuller CA, Vailas AC. A noninvasive analysis of urinary musculoskeletal collagen metabolism markers from rhesus monkeys subject to chronic hypergravity. J Appl Physiol 105: 1255-1261, 2008. First published July 24, 2008 doi:10.1152/japplphysiol.00573.2007.-A decrease in loadbearing activity, as experienced during spaceflight or immobilization, affects the musculoskeletal system in animals and humans, resulting in the loss of bone and connective tissue. It has been suggested that hypergravity (HG) can counteract the deleterious effects of microgravity-induced musculoskeletal resorption. However, little consensus information has been collected on the noninvasive measurement of collagen degradation products associated with enhanced load-bearing stress on the skeleton. The purpose of this study is to assess the urinary collagen metabolic profiles of rhesus monkeys (Macaca mulatta) during 1) 2 wk of basal 1 G (pre-HG), 2) 2 wk of HG (2 G), and 3) two periods of post-HG recovery (1 G). Urine was collected over a 24-h period from six individual rhesus monkeys. Hydroxyproline (Hyp) and collagen cross-links (hydroxylysylpyridinoline and lysylpyridinoline) were measured by reverse-phase HPLC. Urinary calcium, measured by atomic absorption, and creatinine were also assayed. The results indicate no changes in nonreducible cross-links and Hyp during HG. Collagen cross-link biomarker levels were significantly elevated during the 2nd wk of HG. Urinary calcium content was significantly lower during HG than during the 1-G control period, suggesting calcium retention by the body. We conclude that there is an adaptation of the nonhuman primate musculoskeletal system during hyperloading and that noninvasive measurements of musculoskeletal biomarkers can be used as indicators of collagen and mineral metabolism during HG and recovery in nonhuman primates. centrifugation; collagen cross-links; hydroxyproline; Macaca mulatta WELL OVER A CENTURY AGO, Wolff (48) proposed that "change in form and function of bone or of function alone is followed by certain definite changes in their internal architecture . . . in accordance with mathematical laws." This proposal has been extensively studied and modified to a modern proposition, known as the Utah paradigm, that "load-bearing bones are designed to have only enough strength to keep chronically subnormal, normal or supranormal voluntary loads from causing spontaneous fractures" (15, 16). These two propositions imply that actively metabolizing tissues, such as bone, connective tissue, and muscle, should adapt to more or less loading by a change in architecture to be consistent with the load applied.Metabolic by-products of tissue metabolism, measured in urine of astronauts, cosmonauts, and rhesus monkeys, suggest an increase in connective tissue degradation during shortduration exposure to microgravity. The increased urinary excretion of hydroxyproline (Hyp) and mineral salts in astronauts is evidence that degradat...

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