Skeletal calcium homeostasis and countermeasures to prevent disuse osteoporosis

Schneider, Victor; McDonald, Janet

doi:10.1007/bf02406149

Cited by 132 publications

(32 citation statements)

References 8 publications

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“…In addition, these conditions lead to negative calcium balance and loss of bone mineral density (BMD) (11,13,32,33). A similar reduction in musculoskeletal mass has been reported due to the immobilization of extremities seen in external bandaging, casting, or neural resectioning (13,25,27,(39)(40)(41)(42)(43). Both mineralization and collagen metabolism seem to be impaired in animals during the first few days of spaceflight (34).…”

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confidence: 81%

Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI

Wimalawansa¹,

Chapa²,

Wei

et al. 1999

Journal of Applied Physiology

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J. Wimalawansa. Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI. J. Appl. Physiol. 86(6): 1841-1846, 1999.-Microgravity causes rapid decrement in musculoskeletal mass is associated with a marked decrease in circulatory testosterone levels, as we reported in hindlimb-suspended (HLS) rats. In this model which simulates microgravity, we hypothesized that testosterone supplementation should prevent these losses, and we tested this in two studies. Muscle volumes and bone masses were quantitated by using magnetic resonance imaging (MRI) on day 12. In the first study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28.5% of muscle volume (53.3 Ϯ 4.8 vs. 74.5 Ϯ 3.6 cm 3 in the ground control rats; P Ͻ 0.001) and had a 5% decrease in bone mineral density (BMD) (P Ͻ 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and were administered either a vehicle (control), testosterone, or nandrolone decanoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in muscle volume (42.9 Ϯ 3.0 vs. 56 Ϯ 1.8 cm 3 in ground control rats; P Ͻ 0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 Ϯ 2 and 51.6 Ϯ 1.2 cm 3 , respectively; a 63% improvement; P Ͻ 0.05). There were no statistical differences between the two active treatment groups nor with the ground controls. Similarly, there was an 85% improvement in BMD in the testosterone group (1.15 Ϯ 0.04 vs. 1.04 Ϯ 0.04 density units in vehicle controls; P Ͻ 0.05) and a 76% improvement in the ND group (1.13 Ϯ 0.07 density units), whereas ground control rats had a BMD of 1.17 Ϯ 0.03 density units. Because serum testosterone levels are markedly reduced in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses. osteoporosis; microgravity; bone turnover; bone mineral density; anabolic steriod; disuse atrophy DECREMENTS IN BONE AND MUSCLE mass are major concerns in extended space missions (1,8,9,38,49). Immobilization (e.g., bed rest or restricted movements of limbs) can also cause rapid losses in muscle or bone mass (6,9,25,26). Immobilization, prolonged bed rest, and spaceflight conditions inducing microgravity conditions can lead to the general or selective loss of muscle volume and mass. In addition, these conditions lead to negative calcium balance and loss of bone mineral density (BMD) (11,13,32,33). A similar reduction in musculoskeletal mass has been reported due to the immobilization of extremities seen in external bandaging, casting, or neural resectioning (13,25,27,(39)(40)(41)(42)(43). Both mineralization and collagen metabolism seem to be impaired in animals during the first few days of spaceflight (34). Urine analysis in Skylab astronauts has shown a significant loss of minerals, including calcium (10, 37). Reduction of muscle forces leads to a decrease in bone formation and BMD in the os calcis and an i...

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confidence: 81%

Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI

Wimalawansa¹,

Chapa²,

Wei

et al. 1999

Journal of Applied Physiology

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“…This subject has been reviewed previously. [1][2][3][4][5][6][7][8][9] BONE L OSS Bone mineral is lost during spaceflight because weightlessness unloads the skeleton. [10][11][12][13][14][15][16][17] This has been known for decades, but determining predictive factors or showing changes that are consistent from subject to subject has proved difficult.…”

Section: Introductionmentioning

confidence: 99%

Calcium and bone metabolism during space flight

Smith

Heer

2002

Nutrition

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“…Norman et al (2000) reported that moderate aerobic exercise on a treadmill did decrease bone loss caused by hindlimb suspension, however its effectiveness differed by the investigated tissue, anatomical site and parameter. Negative pressure on the lower body, calcitonin, and phosphorus did not prevent negative calcium balance associated with bedrest (Schneider and McDonald, 1984). In contrast, bisphosphonates such as risedronate, alendronate and etidronate have been reported to prevent immobilizationor bed-rest-induced bone loss (Mosekilde et al, 2000; Sc hne i der et a l. , 19 93 ), s u gg es t i ng t ha t p ot en t a n t i r e s o r p t i v e a g e n t s m a y e f f e c t i v e l y p r e v e n t microgravity-induced bone loss.…”

Section: Introductionmentioning

confidence: 99%

A Cysteine Protease Inhibitor Prevents Suspension-Induced Declines in Bone Weight and Strength in Rats.

Nikawa

Ikemoto

Watanabe

et al. 2002

J. Physiol. Anthropol.

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In this study, we examined the effects of a potent cysteine protease inhibitor, N-(L-3-transcarboxyoxirane-2-cabonyl)-L-leucine-4-aminobutylamide (E-64a), on bone weight and strength in tail-suspended rats. We first administered a vehicle or 4 or 8 mg/rat of E64a to rats fed with a low calcium diet for 7 wks to determine effective doses of E-64a on bone resorption in vivo. Femoral cathepsin K-like activity and serum hydroxyproline level in rats fed with a low calcium diet were significantly higher than those in rats fed with a standard diet. The intraperitoneal injection of 8 mg/rat of E-64a to rats decreased their serum calcium and hydroxyproline concentrations after 3 to 6 hrs in parallel with changes in femoral cathepsin K-like activity, while 4 mg/rat of E-64a had weaker effects on these parameters. Based on these results, we injected 8 mg/rat of E-64a to tail-suspended rats twice a day for 2 wks and compared the results with those of treatment with 1 mg/rat of etidronate, a bisphosphonate, twice a week. In tailsuspended rats, femoral weight and strength, assessed by three-point bending test, significantly decreased from Day 5 to 21, while femoral cathepsin K-like activity and serum calcium and hydroxyproline concentrations did not change. E-64a inhibited femoral cathepsin K-like activity in tail-suspended rats, but etidronate did not. E64a as well as etidronate significantly prevented the suspension-induced declines in bone weight and strength. However, more frequent injection and higher doses were required for E-64a to exhibit significant efficacy of antiresorption, compared with those of etidronate. Our results suggest that a cysteine protease inhibitor could improve suspension-induced osteopenia by inhibiting cathepsin K-like activity in bone; however, it needs several improvements in the effect as a clinical drug.

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Skeletal calcium homeostasis and countermeasures to prevent disuse osteoporosis

Cited by 132 publications

References 8 publications

Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI

Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI

Calcium and bone metabolism during space flight

A Cysteine Protease Inhibitor Prevents Suspension-Induced Declines in Bone Weight and Strength in Rats.

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