Degenerative joint disease: An example of calcium paradox

Osteoporosis and degenerative arthropathy such as osteoarthritis and spondylosis deformans represent the two most common diseases seen in later life, sharing some common clinical features such as pain, deformity, and restriction of motion. Augmented bone resorption, possibly mediated by cytokines such as interleukin 1, and favorable therapeutic response to estrogen also characterize both diseases. Both osteoarthritis of the knee and osteoporosis occur frequently in postmenopausal women, whereas spondylosis deformans mainly affects men who experienced a heavy labor load, and women are less susceptible unless they worked as hard as men at some time in their lives. Degeneration of the cartilage with decrease of water content, increase of calcium content, hardening, and subsequent wear and loss would lead to narrowing of the joint space and direct contact of bones, resulting in excessive reactive bone formation such as osteophytes. Because increased physical load on the cartilage and bone would intensify such response, excessive weight and physical exercise always remain important risk factors for degenerative joint disease. The metabolic state precipitating cartilage degeneration, however, may be even more important as the background. Calcium is confined to bone so long as adequate calcium intake is maintained and the hormonal environment remains intact. When calcium deficiency and secondary hyperparathyroidism occur in old age, calcium comes out of bone and starts to accumulate in soft tissues such as blood vessels, brain, and intracellular compartments, where little calcium should be present under normal physiological circumstances. Cartilage should also be devoid of calcium in health, but calcium may accumulate when bone loss occurs in response to estrogen deficiency, calcium deficiency, and secondary hyperparathyroidism. Calcium overabundance prompted by calcium deficiency is known as the calcium paradox. Degenerative joint disease should be included in the group of diseases based on calcium deficiency and calcium paradox, such as hypertension, arteriosclerosis, Alzheimer's disease and other degenerative diseases of the nervous system, diabetes mellitus, and malignancy. Calcium deficiency is thus responsible for both osteoporosis and degenerative joint disease.