Joan M. Muhs

Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women

We report a 4‐year randomized, double‐blind, placebo‐controlled clinical trial in 236 normal postmenopausal women (mean age ± SE, 66.3 ± 0.2 years) who were randomized to a calcium (1600 mg/day as the citrate) or placebo group. The women were seen every 6 months; 177 completed the trial. Net percentage changes in each group are given relative to baseline. The differences in net percentage changes (calcium group minus placebo group) in medians were: for lumbar spine bone density, 2.0% (p < 0.001) at year 1 and 0.3% (not significant) at year 4; for proximal femur bone density, 1.3% (p = 0.003) at year 1 and 1.3% (p = 0.015) at year 4; and for total body bone mineral, 0.4% (p = 0.002) at year 1 and 0.9% (p = 0.017) at year 4. Similar differences at year 4 were: −18.9% (p = 0.002) for parathyroid hormone (PTH), −11.9% (p = 0.026) for serum osteocalcin, and −32.2% (p = 0.003) for urine free pyridinoline. We conclude that long‐term administration of calcium supplements to elderly women partially reverses age‐related increases in serum PTH level and bone resorption and decreases bone loss. However, the effects on bone loss were weaker than those reported for estrogen, bisphosphonates, or calcitonin therapy, indicating that calcium supplements alone cannot substitute for these in treating established osteoporosis. Nonetheless, because of their safety, high tolerance, and low expense, calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age.

Bone Mass and Muscle Strength in Female College Athletes (Runners and Swimmers)

OBJECTIVE To determine whether female college athletes had increased muscle strength and bone mass in comparison with age-matched nonathletic female subjects and, if so, whether participation in weight-bearing versus non-weight-bearing exercise made a difference. MATERIAL AND METHODS We performed a comparative statistical analysis of the bone mineral density (BMD) of the total body, lumbar spine, and femoral neck, maximal oxygen uptake (VO2max), muscle strength, and level of physical activity in 21 runners, 22 swimmers, and 20 control subjects. The study participants were female college students, 18 to 24 years old, who had had more than 8 normal menstrual cycles during the past year. RESULTS Statistical analyses showed significantly higher VO2max in the two athletic study groups than in the control subjects (P < 0.0001). No significant difference in BMD was noted among the three groups. Total body BMD (r = 0.30; P = 0.02) and femoral neck BMD (r = 0.39; P = 0.002) were positively correlated with weight-bearing activity but not with non-weight-bearing activity. VO2Max (an index of physical fitness) was positively correlated with femoral neck BMD (r = 0.33; P = 0.009) and trochanteric BMD (r = 0.29; P = 0.021). Shoulder muscle strength (determined by isokinetic dynamometry) was positively correlated with total body BMD (r = 0.34; P = 0.007) and lumbar spine BMD (r = 0.28; P = 0.028). Swimmers had higher muscle strength in the back and upper extremities than did runners and control subjects. Hip girdle muscle strength was not significantly different among the three groups. Total body BMD had a positive correlation with percentage of body fat and height. Lumbar spine BMD was higher in subjects who had previously used oral contraceptives. The athletes had a lower percentage of body fat, were less likely to have used oral contraceptives, and had fewer years of normal menses than did the control subjects. CONCLUSION Our study shows that (1) total body BMD and femoral neck BMD were significantly higher in the study group that performed weight-bearing exercises than in control subjects, (2) swimming exercise had no effect on BMD, and (3) although swimming is not a bone-building exercise, it can significantly improve shoulder, back, and grip muscle strength.

Mechanism of acute lower extremity pain syndrome in fluoride-treated osteoporotic patients

Acute pain in the lower extremity, which has previously been attributed to synovitis or fasciitis, develops in about 15 percent of osteoporotic patients treated with sodium fluoride. This report describes 11 osteoporotic women in whom this syndrome developed while they were being treated with sodium fluoride (mean dose 78 mg per day; range, 60 to 90). [99mTc]Hydroxymethylene diphosphonate scintiscanning showed an increased number of foci of abnormal uptake in the lower extremities (p less than 0.05), when compared with results of scintiscanning in 12 nonsymptomatic osteoporotic women treated with sodium fluoride and 12 osteoporotic women treated with oral calcium carbonate only. The increased uptake was not restricted to the areas of pain. Roentgenography revealed stress microfractures in five of the 11 symptomatic patients. It is concluded that the acute lower extremity pain syndrome during fluoride therapy usually results from intense regional bone remodeling, which may be complicated by stress microfractures.

Outpatient Percutaneous Biopsy of the Iliac Crest: Methods, Morbidity, and Patient Acceptance

Bone histology and histomorphometry have become important in the diagnosis and management of metabolic bone disease, but the invasive nature of the biopsy procedure has limited its use. We describe an outpatient technique for obtaining one or more transiliac bone biopsy specimens. Thirty-eight women with osteoporosis, each of whom had sustained one or more spinal compression fractures, underwent two separate bone biopsies during which two 7.5-mm transiliac cores of bone were removed. No morbidity (such as infection or hemorrhage) was encountered. Subjective responses to the level of pain were surveyed by questionnaire. At the time of biopsy, 46% of the study subjects experienced no or only mild discomfort, and 24% judged their pain to be severe. At 16 hours after biopsy, 64% had no or mild pain and 8% experienced severe pain. At 7 days after biopsy, 79% experienced no or mild pain but 9% judged their pain to be severe. In four patients, temporary ambulatory disability occurred but resolved spontaneously in 7 to 10 days. We conclude that the described outpatient bone biopsy procedure is safe, efficient, and generally acceptable to patients.

Costs and Strategies in Minority Recruitment for Osteoporosis Research

To meet expectations for the participation of minority populations in research, we committed to enroll 140 minority subjects in addition to a random sample of Olmsted County, Minnesota residents (90% white) for a study of risk factors for age‐related bone loss and fractures. We successfully enrolled 597 additional minority subjects but encountered specific problems with respect to identification of potential subjects, recruitment, obtaining informed consent, transportation to the study site, and collecting study data. These problems were resolved by observing the tenets of outreach to a diverse study population, namely (1) understand the target population; (2) establish explicit recruitment goals; (3) agree on research plans between study staff and minority communities; (4) continuously evaluate the recruitment process; and (5) maintain lines of communication. Success depended especially on the recruitment of cultural advisors from the different ethnic groups. These special efforts increased the recruitment cost substantially; the total expense of

ROLE OF ESTROGEN DEFICIENCY IN PATHOGENESIS OF SECONDARY HYPERPARATHYROIDISM AND INCREASED BONE RESORPTION IN ELDERLY WOMEN

122,000 for recruiting 550 Asian, Hispanic, and Somali subjects was almost 5‐fold higher than the

Effect of Fluoride Treatment on the Fracture Rate in Postmenopausal Women with Osteoporosis

26,000 required to recruit 699 mostly white study subjects from the population who were contacted by mail. Although it is not impossible to recruit minority subjects, investigators (and grant reviewers) should recognize that significant resources are required to gain access to ethnic communities for research. These results should contribute to more realistic budgets for recruiting minority subjects into clinical research studies.

The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women

Whether the increased bone resorption and secondary hyperparathyroidism in elderly women is due to aging or to estrogen deficiency is unclear. To address this issue, we measured serum intact parathyroid hormone (PTH) and biochemical markers in serum and urine samples from 30 premenopausal women (32 +/- 0.5 years, mean age +/- SE), 30 estrogen-deficient postmenopausal women (74.2 +/- 0.6 years), and 30 elderly women (73.8 +/- 0.6 years) receiving long-term estrogen treatment. Because of the first and third groups were comparable in estrogen status but not in age, whereas the second and third groups were comparable in age but not in estrogen status, the independent effects of age and estrogen deficiency could be assessed quantitatively. Mean values were higher in the estrogen-deficient postmenopausal women than in the premenopausal women for serum PTH (by 33%, p < .01) and for bone resorption markers [by 50% p < .001) for urine cross-linked N-teleopeptide of type I collagen (NTx); 34% (p < .001) for urine pyridinoline (Pyd); and 36% (p < .001) for urine deoxypyridinoline (Dpd)]. However, mean values for serum PTH in the postmenopausal women receiving estrogen treatment did not differ from those in the premenopausal women, and mean values for bone resorption markers were not different (urine NTx and Pyd) or were lower [urine Dpd, by -12%, (p < .005)]. These findings suggest that late consequences of estrogen deficiency rather than age-related processes per se are the principal causes of the secondary hyperparathyroidism and increased bone resorption in elderly women.

Clinical trial of fluoride therapy in postmenopausal osteoporotic women: Extended observations and additional analysis

Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.