Exercise and pharmacological countermeasures for bone loss during long-duration space flight.
Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.
Cavanagh
Peter R
PR
Department of Biomedical Engineering, Lerner Research Institute, USA. cavanap@ccf.org
Licata
Angelo A
AA
Rice
Andrea J
AJ
D000337:Aerospace Medicine; D018480:Astronauts; D001510:Bed Rest; D018488:Bone Demineralization, Pathologic / Q000188:drug therapy* / Q000517:prevention & control*; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D001842:Bone and Bones / Q000473:pathology*; D002116:Calcitonin / Q000627:therapeutic use; D002118:Calcium / Q000097:blood / Q000652:urine; D002352:Carrier Proteins; D004164:Diphosphonates / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015914:Estrogen Replacement Therapy; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D010010:Osteoclasts; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013026:Space Flight; D019379:Teriparatide / Q000627:therapeutic use; D014893:Weightlessness / Q000009:adverse effects*; D018544:Weightlessness Countermeasures
D002352:Carrier Proteins; D004164:Diphosphonates; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D020845:Selective Estrogen Receptor Modulators; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D019379:Teriparatide; D002116:Calcitonin; D002118:Calcium