Urinary ovarian and gonadotropin hormone levels in premenopausal women with low bone mass.

We hypothesized that lower ovarian and gonadotropin hormone concentrations would be associated with lower levels of peak bone mineral density (BMD) in apparently normally menstruating women who did not exercise intensively and did not report anorexia or bulimia. This hypothesis was evaluated using a case-with-control study design (n = 65) which was nested within a population-based longitudinal study of peak bone mass (Michigan Bone Health Study) with annual assessment in women aged 25-45 years (n = 582). Cases were 31 premenopausal women with BMD of the lumbar spine, femoral neck, and total body less than the 10th percentile of the distribution, where controls were 34 premenopausal women with BMD between the 50th and 75th percentile. BMD was measured by dual-energy X-ray absorptiometry. In addition to their annual measurement, these 65 participants collected first-voided morning urine specimens daily through two consecutive menstrual cycles. The urine from alternating days of this collection was analyzed for estrone-3-glucuronide (E1G), pregnanediol glucuronide (PdG), testosterone, and follicle-stimulating hormone by radioimmunoassay and these values adjusted for daily creatinine excretion levels. Additionally, analyses of daily urine specimens for luteinizing hormone (uLH) was undertaken to better characterize the possible uLH surge. Cases had significantly lower amounts of E1G (p = 0.009) and PdG (p = 0.002) than did controls, whether amounts were characterized by a mean value, the highest value, or the area under the curve, and after statistically controlling for body size. Further, when B-splines were used to fit lines to the E1G and PdG data across the menstrual cycle, the 95% confidence intervals (CIs) about the line for the controls consistently excluded and excluded and exceeded the 95% confidence bands for the cases in the time frame associated with the luteal phase in ovulatory cycles. Likewise, 95% CIs for the LH surge in controls exceeded the fitted line for cases around the time associates with the LH surge. The cases and controls were not different according to dietary intake (energy, protein, calcium), family history of osteoporosis, reproductive characteristics (parity, age at menarche, age of first pregnancy), follicular phase serum hormone levels, calciotropic hormone levels, or by evidence of perimenopause. We conclude that these healthy, menstruating women with BMD at the lowest 10th percentile from a population-based study had significantly lower urinary sex steroid hormone levels during the luteal phase of menstrual cycles as compared with hormone levels in premenopausal women with BMD between the 50th and 75th percentile of the same population-based study, even after considering the role of body size. These data suggest that subclinical decreases in circulating gonadal steroids may impair the attainment and/or maintenance of bone mass in otherwise reproductively normal women.

Biochemical markers of bone turnover in lactating and nonlactating postpartum women.

We measured two bone-formation markers, osteocalcin and bone-specific alkaline phosphatase, and one bone-resorption marker, N-telopeptide, in a longitudinal study in order to describe levels of these markers in lactating and nonlactating women after parturition. This 18-month postpartum period included an initial 6 months in which a 5% short-term bone loss occurred at both spine and femoral neck among breast-feeding women. The second part of the 18-month period was characterized by bone recovery among women who had lost bone. These bone-change characteristics provided an opportunity to evaluate the performance of biochemical markers during both bone loss and recovery and to identify environmental exposures during lactation associated with bone turnover. The eligible population comprised 115 women whose bone-turnover markers were measured at 2 weeks (baseline) and at 2, 4, 6, 12, and 18 months after parturition. Participants reported reproductive characteristics, diet, physical activity, use of medications, and infant-feeding practices at each contact. Women were grouped according to lactation duration: 0-1 months, 2-5 months, and 6 months or more. Women who breast-fed for at least 6 months had significantly different levels of all three bone-turnover markers compared with the levels in bottle-feeding controls, which were indicative of substantially increased bone turnover. Factors that predicted the difference in biochemical markers from baseline to 6-month values by regression analysis were lactation of 2-6 months duration and lactation for 6 months or more. Dietary calcium intake, physical activity level, and body size did not explain the differences in the change from the baseline level to the 6-month level, a period of time that corresponded with bone loss in the lactating women. Factors that predicted the differences in bone-turnover markers between 6 and 18 months (the time of bone-mass recovery) were lactation status and number of months to resumption of menses. By the 18-month observation, there was no difference in the mean values for the measured bone-turnover markers among the three lactation groups. This suggests that menstrual activity, rather than diet or physical activity, is the primary factor in bone-mass recovery after the bone loss of lactation.

Age-related hearing loss and bone mass in a population of rural women aged 60 to 85 years.

Demineralization of the cochlear capsule in conjunction with age-related bone mass loss may be one biologic factor contributing to hearing loss in the elderly. In other metabolic bone diseases, including Paget's disease of the bone and cochlear otosclerosis, demineralization of the cochlea has been associated with sensorineural hearing loss. In 1988/1989, the relation between hearing loss and bone mass of the radius and femoral neck was studied cross-sectionally in 369 women aged 60 to 85 years from three rural communities. Hearing sensitivity was measured using audiometry, and bone mineral density of the radius and femoral neck was measured using single- and dual-photon densitometry, respectively. Three variables, ascertained by interview, were associated with an increased odds for hearing loss: age, family history of hearing loss before the age of 50 years, and current use of more than two nonestrogen, nonthiazide prescription medications. After consideration of the effect of these three variables, women with femoral neck bone mass values below the mean value of 0.696 g/cm2 for this population had a 1.9 greater odds of having a hearing loss (confidence interval: 1.30, 2.50). This study demonstrated a consistent adjusted association between femoral neck bone mass and age-related hearing loss in a population of rural women aged 60 to 85 years. No consistent association was observed between radial bone mass and hearing loss.

Consistency of perimenopausal estrogen use reporting by women in a population-based prospective study.

The authors assessed the accuracy of perimenopausal estrogen use reporting by 430 women in a prospective study of bone health risk factors. Data from two time points 5 years apart indicated that 383 (89%) women could consistently report having ever used perimenopausal estrogens or not. Of the 383, 138 reported some lifetime perimenopausal estrogen use; 97 (70%) of these consistently reported duration of use. The age-adjusted relative odds that women would misreport having ever used perimenopausal estrogens was 11.7 (1.3, 100.6) for women with 11-20 years since last use, and 22.2 (1.8, 277.4) for 21+ years. Among women who inconsistently reported ever use of perimenopausal estrogen, the relative odds of reporting use at baseline and never use at follow-up as compared to reporting the converse by women aged 70-75 was 8.1 (1.2, 53.2) times that for women aged 60-69 at follow-up, and increased to 9.6 (1.8, 49.9) for women aged 76-85. This suggests that women can consistently report perimenopausal estrogen use, but accurate report of use declines in women whose last use precedes the interview by over 10 years. Accurate report of duration or dates of perimenopausal estrogen use may be compromised in women of more advanced age.

Body size, estrogen use and thiazide diuretic use affect 5-year radial bone loss in postmenopausal women.

Understanding factors associated with more rapid bone mineral loss among aging women is important for establishing preventive strategies for intervention. This study reports factors associated with the 5-year change in radial bone mineral density (BMD) determined prospectively in 435 women aged 55-80 years at baseline. The baseline study included measurement of radial BMD (gm/cm2) by single photon densitometry and personal interview. The baseline protocol was replicated 5 years later in a follow-up study. Women with a lower baseline weight or Quetelet index, smaller triceps skinfold and less arm muscle area had significantly greater 5-year bone loss (p = 0.001). Current users of estrogens had less radial bone loss (2.8% vs 7.3%, p = 0.0005) than women not currently using estrogens. Current users of estrogen had significantly less 5-year loss if use had been for 5 years or longer (-1.0% vs -6.9%, p = 0.05). Current users of the thiazide class of medications had less 5-year radial bone loss (5.0% vs 7.4%, p = 0.0035) than women without current thiazide use. Baseline dietary calcium, alcohol consumption and smoking were not associated with BMD change. This suggests that greater body size, and current use of estrogens or thiazide antihypertensives are associated with less radial bone mass loss in a 5-year period among postmenopausal women.

A prospective study of bone mineral content and fracture in communities with differential fluoride exposure.

In 1983/1984, a study of bone mass and fractures was begun in 827 women aged 20-80 years in three rural Iowa communities selected for the fluoride and calcium content of their community water supplies. The control community's water had a calcium content of 67 mg/liter and a fluoride content of 1 mg/liter. The higher-calcium community had water with a calcium content of 375 mg/liter and a fluoride content of 1 mg/liter. The higher-fluoride community's water had 15 mg/liter of calcium and 4 mg/liter of fluoride naturally occurring. In 1988/1989, a follow-up study characterized the 684 women still living and available for study. Residence in the higher-fluoride community was associated with a significantly lower radial bone mass in premenopausal and postmenopausal women, an increased rate of radial bone mass loss in premenopausal women, and significantly more fractures among postmenopausal women. There was no difference in the 5-year relative risk of any fracture in the higher-calcium community versus the control community; however, the relative risk was 2.1 (95% confidence interval (CI) 1.0-4.4) in women in the higher-fluoride community compared with women in the control community. There was no difference in the 5-year risk of wrist, spine, or hip fracture in the higher-calcium community versus the control community; however, the 5-year relative risk for women in the higher-fluoride community, compared with women in the control community, was 2.2 (95% CI 1.1-4.7). Estimates of risk were adjusted for age and body size.

Longitudinal changes in body composition in women approaching the midlife.

This population-based longitudinal study describes the 4.5-year changes in body composition and body mass distribution in women aged 20-45 years, and characterizes predictors of these changes. Body weight, waist-to-hip ratio, Quetelet index, fat and lean body mass were measured in 404 white menstruating women aged 20-40 at baseline and 4.5 years later (follow-up). Variables considered for predicting body composition differences were hormonal status, menstrual status, parity, diet and physical activity. Average body weight increased 4.3 kg in 4.5 years (6.4 kg increase in fat and 2.1 kg decrease in lean)--a net increase of 7.1% total body fat. Measured predictors were not significantly associated with weight or Quetelet index; however, they were associated with measured amounts of lean and fat. Longitudinally, women who preserved the most lean body mass tended to be nulliparous, to be still menstruating, to have higher testosterone levels, and to smoke. Physical activity was associated with preserving lean body mass. Increasing age and higher follicle-stimulating hormone levels were associated with increasing waist-to-hip ratio. Average body weight showed a steady increase--characterized by an expanding fat compartment and a shrinking lean compartment--with the older women increasing more in waist girth relative to hip girth than younger women. Predictor variables of these changes included hormonal environment, physical activity, smoking behaviour, parity, and oophorectomy.

Bone mineral density in grand multiparous women with extended lactation.

OBJECTIVE: We sought to assess whether the accumulation of multiple, frequent pregnancies and the accompanying repeated extended lactation events was a risk factor for low bone mineral density and osteoporosis. STUDY DESIGN: The study population consisted of 30 grand multiparous women who had borne at least 6 children and lactated for at least 6 months with each child, as well as 6 nulliparous, premenopausal women from a population of Finnish American women associated with the Laestadian Church in Washington State. The Church membership has not embraced contraception or extensive bottle-feeding, resulting in a group of women who are either pregnant or lactating during most of their adult reproductive lives. The medical history included the delivery date, birth outcome, infant birth weight, and number of months lactated for each pregnancy, as well as other health information. Bone mineral density of the lumbar spine, femoral neck, and radius was measured with the Hologic QDR 4500-C dual-energy x-ray absorptiometry scanner. Proc Genmod, SAS version 6.14 (Statistical Analysis Systems, Inc, Cary, NC), was used to perform a Wilcoxon test for a nonparametric analysis of covariance and significance adjusted for age and body size. RESULTS: The 2 study groups did not differ in terms of body mass index, history of smoking, or family history of osteoporosis and fracture, although the parous group was, on average, 8 years older than the nulliparous group (P <.05). The accumulation of repeated pregnancy and lactation events without a recovery interval was not associated with lowered bone mineral density or the presence of osteoporosis or osteopenia. CONCLUSIONS: This study suggests that bone mineral density levels can be sustained in the presence of the rapidly changing hormone environment associated with multiple pregnancies accompanying lactation events without a "recovery" interval.

Familiality and partitioning the variability of femoral bone mineral density in women of child-bearing age.

The contributions of polygenic loci and environmental factors to femoral bone mineral density (BMD) in g/cm2) variability were estimated in modified family sets consisting of women of child-bearing age. Femoral BMDs were measured in 535 women who were members of 137 family sets consisting minimally of an index, her sister, and unrelated female control. The family set could also include multiple sisters and first cousins. Women included in these family sets were all between 20 and 40 years of age to minimize the cohort effects of maturation and menopause on measures of BMD. BMDs were measured at three femoral sites using dual photon densitometry. Values were regressed on age and Quetelet Index which explained 13-15% of the variability in BMD (dependent on site). Subsequent variance components analysis on the residuals indicated that unmeasured polygenic loci accounted for substantial additional variability: 67% for femoral neck, 58% for Wards triangle, and 45% for trochanter. These results suggest that polygenic loci account for approximately half of the variability in maximal femoral BMD.

The associations of bone mineral density and bone turnover markers with osteoarthritis of the hand and knee in pre- and perimenopausal women.

OBJECTIVE: To determine whether Caucasian women ages 28-48 years with newly defined osteoarthritis (OA) would have greater bone mineral density (BMD) and less bone turnover over time than would women without OA. METHODS: Data were derived from the longitudinal Michigan Bone Health Study. Period prevalence and 3-year incidence of OA were based on radiographs of the dominant hand and both knees, scored with the Kellgren/Lawrence (K/L) scale. OA scores were related to BMD, which was measured by dual-energy x-ray absorptiometry, and to serum osteocalcin levels, which were measured by radioimmunoassay. RESULTS: The period prevalence of OA (K/L grade > or =2 in the knees or the dominant hand) was 15.3% (92 of 601), with 8.7% for the knees and 6.7% for the hand. The 3-year incidence of knee OA was 1.9% (9 of 482) and of hand OA was 3.3% (16 of 482). Women with incident knee OA had greater average BMD (z-scores 0.3-0.8 higher for the 3 BMD sites) than women without knee OA (P < 0.04 at the femoral neck). Women with incident knee OA had less change in their average BMD z-scores over the 3-year study period. Average BMD z-scores for women with prevalent knee OA were greater (0.4-0.7 higher) than for women without knee OA (P < 0.002 at all sites). There was no difference in average BMD z-scores or their change in women with and without hand OA. Average serum osteocalcin levels were lower in incident cases of hand OA (>60%; P = 0.02) or knee OA (20%; P not significant). The average change in absolute serum osteocalcin levels was not as great in women with incident hand OA or knee OA as in women without OA (P < 0.02 and P < 0.05, respectively). CONCLUSION: Women with radiographically defined knee OA have greater BMD than do women without knee OA and are less likely to lose that higher level of BMD. There was less bone turnover among women with hand OA and/or knee OA. These findings suggest that bone-forming cells might show a differential response in OA of the hand and knee, and may suggest a different pathogenesis of hand OA and knee OA.

Changes in bone density with lactation.

OBJECTIVE: To test the a priori hypotheses that significant bone loss occurs in lactation of greater than 5 months' duration and that bone mass returns to baseline levels when breast-feeding ceases. DESIGN: Prospective cohort study design of 12 months' duration. SETTING: General community setting with recruitment occurring at birthing education classes. PARTICIPANTS: Volunteer sample of 98 healthy women of white (n = 95) and Asian (n = 3) origin, aged 20 to 40 years, and 0 to 1 parity prior to parturition, grouped according to lactation duration: 0 through 1, 2 through 5, and 6 or more months. MAIN OUTCOME MEASURES: Bone mineral density (BMD) of the proximal femur was measured by dual-energy x-ray densitometry at 2 weeks (baseline), 2 months, 4 months, 6 months, and 12 months following parturition, and BMD of the lumbar spine was measured at baseline, 6 months, and 12 months after parturition. RESULTS: Women with lactation duration of 6 months or longer had mean BMD losses of 5.1% and 4.8% at the lumbar spine and femoral neck, respectively, comparing baseline values with those at 6 months post partum. Women who breast-fed 0 through 1 month lost no BMD at either bone site. Bone loss in women who breast-fed 6 months or longer was not explained by differences in age, diet, body size, or physical activity. Among women who breast-fed 6 months or longer, there was evidence of return to baseline levels of the lumbar spine at 12 months after parturition. The BMD of the lumbar spine of those women who continued to breast-feed more than 9 months had increased but was still significantly lower than baseline. CONCLUSION: Extended lactation (> or = 70% of energy intake is provided for > or = 6 months) is associated with bone loss; however, there is evidence of return to baseline BMD measurement at 12 months after parturition.