Intravenous pamidronate prevents femoral bone loss and renal stone formation during 90-day bed rest.
Long-term bed rest has potential risks of bone loss and renal stone formation. We examined the effects of resistive exercise and intravenous pamidronate on BMD, bone turnover, urinary calcium, and renal stone formation in 25 healthy males during 90-day bed rest. Pamidronate prevented femoral bone loss and renal stone formation, but resistive exercise showed little effects.


BACKGROUND
Long-term bed rest increases the risks of bone loss and urinary stone formation. Resistive exercise increases bone formation, and bisphosphonates reduce bone resorption. However, the effects of muscle exercise and bisphosphonates have not been examined side-by-side. The objectives of this study are to compare the effects of pamidronate with resistive exercise on BMD and renal stone formation during prolonged bed rest.


METHODS
Twenty-five male white volunteers, 26-45 years of age, were randomly assigned to the control (n = 9), exercise (n = 9), and pamidronate (n = 7) groups and underwent 90-day 6 degrees head-down tilt bed rest. Exercise group performed squats and heel raises on a flywheel device for 30 minutes every 3 days. Pamidronate (60 mg) was administered intravenously 14 days before bed rest. BMD of the head, forearm, lumbar spine, and proximal femur; biochemical bone markers; calcium (Ca) metabolism; and abdominal radiographs were examined during 90 days of bed rest and 360 days of reloading.


RESULTS
In controls, proximal femoral BMD decreased, and bone resorption markers and urinary Ca increased during bed rest, along with development of renal stones in two of nine subjects. Resistive exercise increased bone formation but was unable to prevent femoral BMD decrease and increases in bone resorption and urinary Ca during bed rest, with formation of renal stones in four of nine subjects. Pamidronate maintained femoral BMD, reduced bone resorption and urinary Ca, and completely prevented renal stone formation.


CONCLUSIONS
Resistive exercise increased bone formation but could not reduce bone resorption and the risk of renal stones. In contrast, inhibition of bone resorption by pamidronate could preserve bone mineral and reduce the risk of renal stone formation during prolonged bed rest.
Test Facilities Operation and Maintenance Section, Space Station Engineering Department, Advanced Engineering Services, Co., Ltd., Ibaraki, Japan.
Yukiko
Y
Watanabe
Hiroshi
H
Ohshima
Koh
K
Mizuno
Chiharu
C
Sekiguchi
Masao
M
Fukunaga
Kenjiro
K
Kohri
Jörn
J
Rittweger
Dieter
D
Felsenberg
Toshio
T
Matsumoto
Toshitaka
T
Nakamura
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001510:Bed Rest; D015415:Biomarkers; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000517:prevention & control*; D016723:Bone Remodeling / Q000502:physiology; D001862:Bone Resorption; D001842:Bone and Bones; D002118:Calcium / Q000652:urine; D004032:Diet; D004164:Diphosphonates / Q000008:administration & dosage* / Q000494:pharmacology*; D015444:Exercise; D005080:Exercise Test; D006801:Humans; D007262:Infusions, Intravenous; D007669:Kidney Calculi / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D000077268:Pamidronate; D016683:Supine Position; D013997:Time Factors
D015415:Biomarkers; D004164:Diphosphonates; D000469:Alkaline Phosphatase; D000077268:Pamidronate; D002118:Calcium