RAREFYING DISEASE OF THE SKELETON 439 



Twenty-two cases, previously free of fractures, did not acquire 

 collapsed vertebrae, and had onlv a physiologic rate of decline in 

 bone density. These observations suggested that spontaneous col- 

 lapses of vertebrae are indicative of structural hone failure, and 

 this is the cardinal sign of osteoporosis. Bone failure distinguishes 

 the disorder from physiologic bone atrophy of the aging. Bone fail- 

 ure occurs when bone mass declines more rapidly than normal to 

 50 per cent of the quantity that is found in voung adult women. 



3. The morphologic and biochemical indices of aging are qualita- 

 tively the same, but quantitatively more extreme in osteoporotics 

 than in nonosteoporotics. Many osteons stop growing and calcifying 

 and develop a sclerotic inner margin before they are one-half closed. 

 Bone cells retract, enlarge the lacunae, and disappear in the outer 

 and interstitial lamellae that are farthest from the blood vessel. The 

 matrix becomes more basophilic, metachromatic, and irregular stain- 

 ing. These morphologic and histochemical changes are unspecific, 

 but are approximately 30 to 50 per cent more extreme during middle- 

 aged life in patients with severe osteoporosis. As much as 50 per 

 cent of the bone tissue in the tibia mav be dead. 



4. The recent literature may be interpreted to propose a unifying 

 hypothesis that extreme dietary deficiencies of calcium and protein, 

 various endocrinopathies, and many degenerative vascular system 

 disorders produce premature or accelerated aging of bone, and that 

 osteoporosis appears as a result. The conditions responsible for reten- 

 tion of bone or the maintenance of an antiosteoporosis factor that 

 regulates the physiologic rate of aging of the skeleton are possibly 

 related to the genetic constitution of the individual, but otherwise 

 are entirely unknown. 



5. A regimen of vigorous constitutional exercises, including deep 

 breathing, bicycling, swimming, and hiking, should be added to 

 medical or orthopedic treatment to improve the circulation and 

 retention of bone in the aging and osteoporotic skeleton. 



Acknowledgments. These investigations were supported by Contract 

 No. AT(04-1)-GEN-12 between the Atomic Energy Commission and the 

 University of California Medical Center, Los Angeles, and by grants-in- 

 aid from the National Institutes of Health, United States Public Health 



