Changes in markers of bone formation and resorption in a bed rest model of weightlessness

Lueken, Sandra A.; Arnaud, Sara B.; Taylor, A.; Baylink, David J.

doi:10.1002/jbmr.5650081204

Cited by 112 publications

(32 citation statements)

References 21 publications

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“…In the present study, the levels of urinary Hyp were elevated during Rec-2, suggesting that resorption or ECM turnover was increased during the later stages of HG and through the recovery periods. In support of our study, urinary Hyp levels were increased by reduced ground reaction forces experienced by patients in bed-rest studies and remained elevated for a period after reambulation (25). It is our hypothesis that, during a decrease in load-bearing activity in the musculoskeletal system, such as immobilization and/or spaceflight, Hyp is derived from resorption from connective tissues (catabolism), whereas adaptation to a chronic HG perturbation, as shown in this HG study, may result in a delayed connective tissue loss followed by urinary Hyp excretion to a new level of basal homeostasis or, perhaps, new ECM formation (anabolism).…”

Section: Collagensupporting

confidence: 86%

“…Data collection continued throughout the postcentrifugation recovery period (recovery 1 G, days . The chronic HG period and the recovery 1-G period were further subdivided at or near the midpoints during the respective timelines into two subperiods: HG-1 wk (days 16 -22) and HG-2 wk (days [23][24][25][26][27][28][29][30] and Rec-1 (days 31-41) and Rec-2 (days 42-51).…”

Section: Experimental Designmentioning

confidence: 99%

“…An increase in urinary Hyp excretion has been reported in astronauts after 84 days of spaceflight (42), and increases in urinary Hyp levels have also been reported in patients subjected to 7 days of bed rest (25). Increased levels of urinary Hyp suggest that microgravity and bed rest may cause an increase in bone resorption and resorption of collagen from other connective tissue sources (25,42). Although Hyp is commonly used as a bone metabolism marker, it is not specific to bone (3,25).…”

Section: Collagenmentioning

confidence: 99%

“…Increased levels of urinary Hyp suggest that microgravity and bed rest may cause an increase in bone resorption and resorption of collagen from other connective tissue sources (25,42). Although Hyp is commonly used as a bone metabolism marker, it is not specific to bone (3,25). Thus the increase in Hyp levels during HG may be due to resorption in other tissues containing collagen, in addition to bone.…”

Section: Collagenmentioning

confidence: 99%

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

Martinez

Patterson-Buckendahl²,

Lust³

et al. 2008

Journal of Applied Physiology

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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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Section: Collagensupporting

confidence: 86%

Section: Experimental Designmentioning

confidence: 99%

Section: Collagenmentioning

confidence: 99%

Section: Collagenmentioning

confidence: 99%

See 2 more Smart Citations

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

Martinez

Patterson-Buckendahl²,

Lust³

et al. 2008

Journal of Applied Physiology

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show abstract

“…The factors that affect bone metabolism after fracture are the invasiveness of surgery, the period of bed rest, the degree of fracture, immobilization, and the process of fracture healing [7,12,17,26,31]. In our study groups, there were no differences in the period of bed rest and BMD of the femoral neck.…”

Section: Discussionmentioning

confidence: 56%

Sequential Changes of Bone Metabolism in Normal and Delayed Union of the Spine

Ohishi

Takahashi

Yamanashi

et al. 2008

Clinical Orthopaedics &Amp; Related Research

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Time-dependent changes in bone markers in delayed or nonunion of vertebral fracture were compared with those of normal union. Thirty-three patients with a fresh vertebral fracture were enrolled. Urinary Type I collagen C-terminal telopeptide, pyridinoline, deoxypyridinoline, serum C-terminal telopeptide, and N-midportion of osteocalcin (OC N-mid ) were determined at the time of hospital admission (within 24 hours after the fracture event in all cases) and at 2, 4, 12, 24, and 48 weeks thereafter.

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Expression of osteocalcin in the patella of experimentally immobilized and remobilized rats

Kannus

Józsa²,

Kvist

et al. 1996

Journal of Bone and Mineral Research

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The exact mechanisms by which mechanical loading-unloading affects bone tissue are mostly unknown. Recently, osteocalcin, a direct product of osteoblasts, has been shown to reflect the activity of the mineralization phase of the newly formed bone matrix, and therefore, the in situ detection of osteocalcin could be used for studying the effects of physical activity-inactivity on the osteoblast function or bone formation in the target bone. In this study, the effect of various loading states (immobilization and three forms of subsequent remobilization) on the in situ expression of osteocalcin in the rat patellas and their osteotendinous junctions was studied immunohistochemically using a polyclonal rat antiosteocalcin as the primary antibody. Following immobilization for 3 weeks, the immunoreactivity of osteocalcin was markedly decreased or was completely absent in all the patellar areas which normally show intense reaction as a sign of mineralization of the newly formed bone, that is, in the subperiosteal and subchondral regions, in the osteoid tissue that lies on the surface of the trabecular bone, and around the cortical lacunae. The same was true in the mineralized fibrocartilage zone of the osteotendinous junction of the quadriceps tendon. Free remobilization for 8 weeks (free cage activity) could not improve the situation, but after intensified remobilization of the same duration (low and especially high intensity treadmill running) high osteocalcin expression was observed in the above-mentioned anatomic sites. These findings indicate that formation of new bone tissue is rapidly regulated by the loading states of the bone. Higher than normal activity seems to be needed to restore the bone formation from the disuseinduced depression to normal.

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Changes in markers of bone formation and resorption in a bed rest model of weightlessness

Cited by 112 publications

References 21 publications

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

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

Sequential Changes of Bone Metabolism in Normal and Delayed Union of the Spine

Expression of osteocalcin in the patella of experimentally immobilized and remobilized rats

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