OSTEOPOROSIS: EPIDEMIOLOGY, PREVENTION AND CAUSATIVE MECHANISMS
Osteoporosis is an age-related reduction in bone mass and density that ultimately increases a person's susceptibility to fractures. Hip fractures were associated with a 20% increase in overall mortality and 300,000 hospital admissions in 1995. Moreover, health costs necessary to manage fractures that year exceeded 13.8 billion dollars.
Bone loss is continual with aging in the sedentary individual. Women reach frailty before men because they start with smaller bones at the age of 30 years, and they lose the estrogen-promotion of bone accretion at menopause. The percentage of individuals over 65 years of age having osteopenia (reduced bone density) and osteoporosis (more severely reduced bone density) is very high. Osteoporosis is especially pronounced in women: 50% of women older than 85 have osteoporosis, compared to only about 10% of men the same age. This disorder does develop in men, but at a much delayed rate.
Epidemiological data indicates that bed rest markedly accelerates bone loss. Significant quantities of bone mineral were lost in healthy subjects after 17 weeks of bed rest. The amount of loss seems to be greatest caudally. Immobilized patients can lose up to 40% of their original bone mineral density in 1 year, whereas standing upright for as little as 30 minutes per day prevents this bone loss.
Primary Prevention of Osteoporosis
Current evidence indicates that three environmental factors accelerate bone loss:
• Physical inactivity
• Insufficient nutrient and calcium intake
• Reduced female reproductive hormones.
Physical inactivity speeds the onset of osteoporosis with aging. Broken hips in elderly individuals are associated with increased mortality.
The results from the National Osteoporosis Risk Assessment (NORA) indicate that people who have a history of regular exercise have a significantly reduced risk of developing osteoporosis. Appropriate physical activity, such as a chronic loading type, delays osteoporosis and prevents loss of bone mass.
Low bone mineral density (BMD) is the single best predictor of fracture risk. The formation of new bone occurs through the sensation of strain imposed via an unaccustomed direction or distribution. In fact, exercise intervention programs have found increases of 1-5% in BMD in young populations. In the elderly, load-bearing exercise interventions can increase BMD by 5-8%. Although not all studies indicate that exercise programs can increase BMD, most do suggest that load-bearing activities such as standing, walking, and resistance training can reduce the rate of bone loss, and thereby maintain bone mass during aging.
As bone mass peaks around the age of 20, primary prevention means that increases in bone mass must be emphasized in childhood and adolescence, i.e., factors detrimental to the addition of bone mass in development should be avoided. After the second decade of life, emphasis needs to be placed on maintaining existing bone mass.
Secondary Prevention of Osteoporosis
Though bed rest significantly depletes bone mineral, recovery is possible (albeit incomplete) with re-ambulation and load bearing. Bone mineral recovered only partially after 17 weeks of bed rest in healthy 35-year-old male subjects who re-ambulated for 6 months. The trochanter only regained 26% of its lost bone mineral, meaning that it had 3.4% less bone mineral than prior to the 17 weeks of bed rest. Similar results were noted for the femoral neck and lumbar spine, which recovered 0% and 16%, respectively. This represents a deficit of 3.6% and 3.2 % of bone mineral even after 6 months of re-ambulation.
Tertiary Prevention of Osteoporosis
It is easier to lose bone mass than to regain it after the loss. Specifically, much work is required to regain small amounts of bone mass, especially if the mass is lost due to complete immobility or a sedentary lifestyle. More bone mass is lost during the condition of immobility (due to lack of loading) than in the sedentary state (minimal activity). Walking slows the loss, and high-impact loading can actually increase bone mass. Clinical conditions producing complete immobility must be addressed with primary preventive measures to minimize bone loss, and secondary and tertiary preventive measures to recover lost bone mineral.
Mechanical strain, such as that encountered during high-impact loading activities and strength/resistance exercises, increases bone formation. According to Wolf's law, bone remodels itself to adapt to increased loads by altering its mass and distribution of mass.
Osteoporosis occurs when bone resorption exceeds bone formation. The increase in IGF-I mRNA and protein expression is consistent with the model that IGF-I generated by osteoblasts in response to mechanical loading may participate in the induction of bone formation, by its ability to induce proliferation and differentiation of osteoblastic cells in culture.
Prostaglandins are produced very early after the administration of mechanical strain in osteoblastic cells. Also, compounds that induce the production of nitric oxide (NO) increase the rate of new bone formation during mechanical loading. There are multiple isoforms of NO synthase (NOS). Expression of endothelial NOS in osteoblasts and osteocytes has been observed, and been shown to be sufficient to stimulate proliferation of osteoblasts in cell culture. The precise links between these processes, however, remain unclear.