Faculty Bibliography

Eighty white women, mean age 52 years, within one to six years postmenopausal, were studied to examine the relationship of various factors to bone mass. Forty-four of the women had annual measurements of bone mass, so that the rate of bone loss could be determined. Bone mass was measured by total body neutron activation analysis and photon absorptiometry of the distal radius (total body calcium [TBCa] and bone mineral content [BMC], respectively). Breast-feeding and pregnancy were noted to be associated with higher bone mass; those with lower BMC and/or TBCa tended to have higher serum alkaline phosphatase levels, lower testosterone levels, and more years since the cessation of menses. The rate of bone loss from the radius was greater in those with higher parathyroid hormone levels; those with reduced dietary intake of calcium and lower 25-hydroxyvitamin D levels had a greater rate of loss of TBCa.

The sodium excess (Naes) which represents the nonexchangeable sodium compartment of bone was calculated from the total body sodium and total body chlorine of 95 women with vertebral crush fracture syndrome. No evidence was found for a subpopulation with increased or decreased Naes or Naes:TBCa ratio (TBCa is total body calcium which reflects total skeletal mass). Correlations in the osteoporotic women were found between the Naes and serum alkaline phosphatase (r = 0.31), PTH (r = 0.53), urinary hydroxyproline excretion (r = 0.42) and serum 250H vitamin D (r = -0.32). These data suggest that the state of vitamin D nutrition as well as parathyroid hormone levels may influence the quantity of sodium in bone in osteoporotic women. It is of great interest that these relationships were not observed in two control populations consisting of elderly women and women who recently underwent spontaneous menopause.

A 17-year-old girl with thalassemia major experienced tetany. The serum calcium level was 5.5 mg/dL, and the phosphorus level was 6.3 mg/dL. Serum levels of parathyroid hormone (PTH) and 25-hydroxyvitamin D (25-OHD) were subnormal at 125 pg/mL and 8.1 ng/mL, respectively, As a result of these findings, serum 25-OHD and PTH levels were measured in an additional 12 patients with thalassemia major. Low levels of both 25-OHD and PTH were found frequently. An increase in serum 25-OHD levels was noted in each of four patients who were examined after iron chelation therapy.

Regional and total bone mass were determined in three groups of women by photon absorptiometry of the distal radius [bone mineral content BMC)] and total body neutron activation analysis [total body calcium (TBCa)], respectively. There were three groups of patients: group A, osteoporotic women treated with a variety of pharmacologic agents; group B, osteoporotic women (controls) taking only calcium supplements; and group C, normal postmenopausal women. The mean TBCa and BMC were considerably higher in the postmenopausal women than in the osteoporotic women. The rate of change of bone mass in group C was -0.45%/yr and -0.9%/yr for the total skeleton and radius, respectively. Group B had no significant rate of loss, whereas group A demonstrated a significant increase in TBCa of 0.75%/yr with no change in the BMC of the radius. There were no significant between-subject correlations for the slopes (rates of change) of the two bone mineral measurements.

Nine women with postmenopausal spinal osteoporosis were treated with combination therapy consisting of estrogen, fluoride, and calcium. Their data were compared with those of a control group treated with fluoride, and calcium without estrogen. Bone mass was measured about every six months by photon absorptiometry (bone mineral content/bone width (BMC/BW)] and total-body neutron activation analysis [total-body calcium (TB Ca)]. Time-trend analysis revealed positive slopes for TB Ca (P = 0.002) and BMC/BW (P = N.S.) for the combination therapy group. The change in BMC/BW in the combination therapy group was significantly different from the response in the fluoride - calcium group. These data suggest that combination therapy may be successful in increasing bone mass in postmenopausal osteoporosis. A clinical trial to establish efficacy and examine risk/benefit ratios should be performed.

A two compartment, double-blind, randomized, parallel study was performed comparing methandrostenolone with placebo in the treatment of osteoporosis. The duration of the study was 24 mo. Dependent parameters included total body calcium (TBCa), measured by neutron activation analysis: bone mineral content of the radius (BMC), measured by photon absorptiometry; and total body potassium (TBK), measured by total body counting. A significant increase in TBK occurred in the treated group, primarily in the first 6 mo; thereafter the TBK remained fairly constant. No significant changes in bone mass occurred, except the 6 mo TBCa measurement increased by 11 grams for the methandrostenolone group and decreased by 6 grams for the placebo group (p = .05). Other evidence also suggests that anabolic steroids may not produce sustained uncoupling of bone formation and bone resorption in osteoporosis. If methandrostenolone is capable of producing an increment in bone mass in osteoporosis, it was not readily observable with the sensitivity of the techniques employed in this study

Involutional osteopenia contributes to older persons' susceptibility to fractures of the hip, spine and wrist. Experimental evidence is reviewed that supports the hypothesis that involutional bone loss can be prevented by physical exercise. Weightlessness and immobilization result in accelerated bone loss. In cross-sectional studies measuring total body potassium (TBK), both muscle mass and bone mass in normal humans have remained strikingly constant. The usual decrease in total body calcium (TBCa) and TBK with increasing age was not observed in a cross-sectional study of marathon runners. Localized hypertrophy of bone and muscle has been reported for a variety of occupations and sports. Two prospective studies have demonstrated an increment in bone mass after a program of physical exercise. It would seem that certain involutional changes in body composition (loss of TBCa and TBK) can be prevented by increased physical activity, but the effectiveness of specific types and durations of exercise should be investigated.