Osteoporosis: new markers
for an old disease
Author:
Laxmi Srivastava, DVM, Ph.D., Professor
Osteoporosis currently affects more than 25 million people in the United States and this number is expected to increase as the "baby boomers" age. The National Institute on Aging estimated in 1987 that expenditures to control the disease and to treat the chronic misery of the affected patients exceeded $10 billion a year. It is, therefore, vital to find a marker which can both detect osteoporosis at an early age before any damage is done as well as assess the effectiveness of therapy.
Osteoporosis, or porous bone, is a disorder of skeletal fragility that predisposes the patient to a greater risk of non-traumatic fracture. It is characterized by low bone mass and structural deterioration of bone tissue leading to greater susceptibility to features particularly of the hip, spine, and wrist. Women's risk is four times that of men. Loss of estrogen production at menopause results in increases in bone turnover with resorption usually exceeding formation in a net loss of bone. It is estimated that half of all postmenopausal women in the U.S. are likely to develop this disease. Two categories of bone markers are currently being evaluated:
During bone formation an organic matrix is laid down and mineralized with calcium phosphate by cells called osteoblasts. As new bone is formed, osteocalcin and alkaline phosphatase are released into the bloodstream. Each can be used as a measure of bone formation.
Bone resorption is a function of the osteoclasts. These cells remove the mineral from bone and break down the organic matrix, which is primarily comprised of collagen, into smaller fragments. One of these fragments, cross-linked N-telopeptides of type I collagen (NTx), is the link that normally holds the helical strands of bone collagen together at the N-terminus and gives collagen its strength and resiliency. Because the NTx assay measures bone loss through collagen breakdown products, it is a dynamic, real-time measure of metabolic changes. It, therefore, has the potential to greatly enhance the clinician's ability to immediately identify abnormal bone loss conditions and to track the efficacy of treatment strategies. The specificity of the NTx assay lies in the fact that the sequence which is being measured is unique to type I collagen which is part of the bone. An NTx urine assay is very specific and provides a quantitative measure of bone resorption whereas measurements of calcium, pyridinolines, or hydroxy-proline (Pyrilinks), can be affected by connective tissue and diet.
Excretion levels of bone resorption markers, such as NTx have been evaluated to determine whether patients at risk for osteoporosis can be identified. Of interest is the possibility that a combination of bond density measurement with NTx might predict the rate of bone loss thus aiding the physician in determining the type and dos of drugs need ed for therapy as well as determine patient compliance with hormone-replacement and other osteoporosis therapies. Figure 1 is an outline of the National Osteoporosis Foundation guidelines for prevention, evaluation and treatment of osteoporosis with antiresorptive therapy.