Bone Mass, Bone Metabolism, Gonadal Status and Body Mass Index

Weight and gonadal status are the main determinants of bone mass in women. Because of this it is important to study which influences it more. The effect of weight (expressed as body mass index, BMI) and gonadal status of women on total-body bone mineral content (TBBMC) and regional bone mineral content (BMC) was investigated. A total of 373 normal women (mean age 48.9 ± 13.4 years) were studied: 171 postmenopausal women (mean age 59.3 ± 9.5 years; years since menopause 11.3 ± 6.7 years); 76 perimenopausal women (mean age 48.9 ± 2.2 years); and 126 premenopausal women (mean age 34.7 ± 7.4 years). In all the women, TBBMC and regional BMC were determined by dual-energy X-ray absorptiometry. Also biochemical markers of bone metabolism (total alkaline phosphatase and tartrate-resistant acid phosphatase) and serum estrone and estradiol were determined. When the women were stratified by gonadal status and BMI, thin women (BMI <20 kg/m²) had significantly lower TBBMC and regional BMC, lower gonadal steroid concentration and higher levels of biochemical markers than overweight (BMI 25–30 kg/m²) and obese (BMI >30 kg/m²) women, regardless of gonadal status. Overweight and obese women had findings suggestive of increased parathyroid activity, but greater bone mass. Weight rather than gonadal steroid concentration is the main determinant of bone mass in women regardless of gonadal status. Received: 6 July 2001 / Accepted: 15 November 2001     

Risk Factors for Perimenopausal Distal Forearm Fracture

This prospective population-based cohort study investigated factors predicting distal forearm fracture (DFF) in perimenopausal women. The study population consisted of 11 798 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study in Finland. Mean baseline age of these women was 52.3 (SD 2.9) years (range 47–56 years) and 68% were postmenopausal. Three hundred and sixty-eight women (3.1%) had a validated DFF during the 5-year follow-up. Previous wrist fracture, postmenopausal state, age and nulliparity were independent predictors of DFF, while hormone replacement therapy (HRT), dairy calcium and overweight protected against it in multivariate Cox regression analysis: previous wrist fracture increased the DFF risk by 158% (p<0.0001), menopause by 69% (p= 0.002) and age by 6% per year (p= 0.010), whereas the continuous use of HRT decreased the risk by 63% (p= 0.0001), the use of dairy calcium at 1000–1499 mg/day (vs <500 mg/day) by 39% (p= 0.004), overweight (BMI >25 kg/m²) by 36% (p= 0.0002) and parity by 29% (p= 0.031). Combining dichotomous low weight, low use of calcium, non-use of HRT and previous wrist fracture into a risk score gave a dose–response effect by score level: the presence (vs absence) of all four risk factors resulted in a 12-fold DFF risk. Nevertheless, the sensitivity and specificity of the score for detecting DFF remained low. It was concluded that HRT, high nutritional calcium intake and overweight protect against but a history of wrist fracture predisposes to perimenopausal distal forearm fracture. A simple risk factor inquiry would help to identify perimenopausal women at high risk of distal forearm fracture. Received: 7 July 1999 / Accepted: 6 September 1999     

Not All Postmenopausal Women on Chronic Steroid and Estrogen Treatment are Osteoporotic: Predictors of Bone Mineral Density

Chronic steroid use results in osteoporosis, and postmenopausal women are believed to be at a high risk for steroid-induced bone loss. The purpose of this study was to determine predictors of bone mineral density (BMD) in postmenopausal women on both chronic steroid and hormone replacement therapy. Seventy-six postmenopausal women (≥3 years postmenopausal, ≥2 years of steroid treatment of ≥5 mg/day of prednisone, and ≥1 year of hormone replacement therapy) were recruited into this study. Measurements of BMD of the lumbar spine and femoral neck were obtained in all subjects. Risk factors for osteoporosis were obtained by questionnaire. Discriminant analysis was performed to determine predictors of BMD. Osteoporosis, defined by a T score of <−2.5, was present in the lumbar spine or femoral neck in 34 of the 76 subjects. Based on these criteria, women with osteoporosis were significantly older, were more years postmenopausal, and had a lower body mass index (BMI) than women who did not have osteoporosis. Predictors of osteoporosis for both the femoral neck and spine included a low BMI (P < 0.05), more years postmenopausal (P < 0.01), and more years on steroids (P < 0.01). Low BMI was the only significant predictor of osteoporosis in the lumbar spine (P < 0.05), whereas for the femoral neck both years on steroids (P < 0.05) and BMI (P < 0.05) were significant predictors of low BMD. In summary, not all postmenopausal women on chronic steroid and hormone replacement therapy are osteoporotic but a low BMI, more years on steroids, and more years postmenopausal were significant predictors of osteoporosis in these subjects. Received: 8 November 1997 / Accepted: 21 May 1997     

The Effect of Weight Change on DXA Scans in a 2-Year Trial of Etidronate Therapy

Variation in soft tissue composition is a potential cause of error in dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD). We investigated the effect of patients' change of weight on DXA scans in 152 women enrolled in a 2-year trial of cyclical etidronate therapy. Scans of the spine, hip, and total body were performed at baseline, 1 and 2 years on a Hologic QDR-2000. The study was completed by 135 subjects (64 on etidronate, 71 on placebo). Results were expressed as the percentage change in BMD (spine, femoral neck, total body) or bone mineral content (BMC) (total body only) at 2 years. Total body scans were analyzed using the manufacturer's `standard' and `enhanced' algorithms. Analysis was performed using multivariate regression with percentage change in BMD or BMC as the dependent variable, and treatment group and percentage change in weight as the independent variables. Weight change varied between −14.4% and +16.7%. All DXA variables showed a statistically significant treatment effect. Standard total body BMD and BMC and enhanced total body BMC all showed a significant dependence on weight change (P < 0.01, P < 0.001 and P < 0.01, respectively). No effect of weight change was seen on spine, femoral neck, or enhanced total body BMD. In order to investigate the effects of weight on long-term precision, patients were allocated to two groups according to baseline body mass index (BMI <25 and >25 kg/m², respectively). For femoral neck BMD the root mean square (RMS) residual percentage change was statistically significantly larger in the high BMI group (P < 0.05) but all other bone density variables showed no significant difference. With patients allocated to two groups according to their absolute percentage change in weight (<5% and >5%, respectively) the RMS residual percentage changes in the bone density variables were statistically significantly larger in the large weight change group for femoral neck BMD (P < 0.05) and for standard and enhanced total body BMC (P < 0.01 and P < 0.05, respectively). With the exception of the standard total body algorithm, weight change in a longitudinal study of postmenopausal women was not found to cause systematic errors in the results of DXA studies but may adversely affect precision. Received: 22 November 1996 / Accepted: 30 April 1997     

Reduced Bone Mass and Fat-Free Mass in Women with Multiple Sclerosis: Effects of Ambulatory Status and Glucocorticoid Use

Multiple sclerosis (MS) is associated with reduced bone mass and vitamin D deficiency. The underlying pathophysiology of the bone disease is uncertain, however, acute and long-term glucocorticoid use, progressive immobilization, vitamin D deficiency, and possibly skeletal muscle atrophy are likely to be determinants. The aims of this study were to determine (a) whether multiple sclerosis is associated with reduced fat-free mass and (b) whether in patients with multiple sclerosis, ambulation ability or glucocorticoid use is associated with bone mass and/or fat-free mass. Seventy-one female patients with MS were compared with 71 healthy, age-matched female controls. Total body bone mineral content (TBBMC, kg), fat mass (FM, kg), and fat-free mass (FFM, kg) were measured using dual X-ray absorptiometry. Disability status was graded according to the Kurtzke Expanded Disability Status Scale (EDSS) as ambulatory, with or without aide (EDSS score of 0 to 6.5), or predominantly wheelchair bound (EDSS score > 6.5). The patients with MS, when compared to age-comparable controls, had deficits in TBBMC (≈ 8%, −0.3 ± 0.1 SD, P < 0.04) and FFM (≈ 5%, −0.3 ± 0.1 SD, P < 0.01). Both TBBMC and FFM were negatively associated with EDSS score (r= 0.33, P < 0.01, and r= 0.41, P < 0.01, respectively). Patients with MS who were nonambulatory had even greater deficits in TBBMC and FFM as compared with age-matched controls (−0.6 ± 0.1 SD, P < 0.01, and −0.6 ± 0.1 SD, P < 0.01, respectively). By contrast, as compared with age-comparable controls, ambulatory patients with MS had no deficits in bone mass or soft tissue mass. When compared with ambulatory patients with MS, nonambulatory patients with MS had deficits in TBBMC and FFM (P < 0.01 and P < 0.01, respectively). The difference in TBBMC was largely caused by the difference in fat-free mass, whereas the difference in FFM was largely caused by the difference in glucocorticoid use based on analysis of covariance. We conclude that in patients with multiple sclerosis, physical disuse is the main determinant for the reduction in bone mass. Glucocorticoid treatment is the major determinant of the reduction in fat-free mass and thus also contributes to the reduction in bone mass. Received: 8 July 1996 / Accepted: 31 October 1996     

Loss of Bone Mineral Density in Women Athletes During Aging

Total and regional bone mineral density (BMD) by dual-energy-X-ray absorptiometry (DXA) and bone turnover were tested in 50 highly trained women athletes and 21 sedentary control women (18–69 years; BMI < 25 kg/m²). VO_2max (ml · kg⁻¹· min⁻¹) and lean tissue mass (DXA) were significantly higher in the athletes versus controls (both P < 0.0001). Total body BMD did not decline significantly with age in the athletes whereas lumbar spine (L₂–L₄) BMD approached statistical significance (r =−0.26; P= 0.07). Significant losses of the femoral neck (r =− 0.42), Ward's triangle (r =−0.53), and greater trochanter BMD (r =−0.33; all P < 0.05) occurred with age in the athletes. In the athletes, total body BMD, L₂–L₄ BMD, and BMD of all sites of the femur were associated with lean tissue mass (r = 0.32 to r = 0.57, all P < 0.05) and VO_2max (r = 0.29 to r = 0.48, all P < 0.05). Femoral neck and greater trochanter BMD were higher in the athletes than in controls (both P < 0.05) and lumbar spine and Ward's triangle BMD approached statistical significance (both P= 0.07). Bone turnover was assessed by serum bone-specific alkaline phosphatase (B-ALP), urinary deoxypyridinoline cross-links (Dpd), and urinary aminoterminal cross-linked telopeptides (NTX). There were no relationships between B-ALP or Dpd with age whereas NTX increased with age (r = 0.46, P < 0.05) in the entire group. Levels of B-ALP and NTX were negatively associated with total body, L₂–L₄, femoral neck, Ward's triangle, and greater trochanter BMD (P < 0.05). B-ALP and Dpd were not significantly different between athletes and controls whereas NTX was lower in the athletes than in controls (P < 0.001). The high levels of physical activity observed in women athletes increase aerobic capacity and improve muscle mass but are not sufficient to prevent the loss of bone with aging. Received: 28 November 1997 / Accepted: 8 April 1998     

Association Between Female Sex Hormones and Biochemical Markers of Bone Turnover in Peri- and Postmenopausal Women

In an epidemiological study, markers of bone formation (serum osteocalcin and C-terminal propeptide of type I collagen) and bone resorption [urinary type I collagen peptides (Crosslaps), urinary total pyridinoline (TPYRI), urinary deoxypyridinoline (DPYRI) as well as female sex hormones (serum estradiol)], follicle-stimulating hormone (FSH) and luteinizing hormone were measured in 237 women. This cohort aged 44–66 years, came for their first medical examination since menopause to the outpatient menopause clinic at the Kaiser-Franz-Josef-Hospital, Vienna. The women were all 0.5–5.0 years since cessation of menses and were not taking medications other than hormone replacement therapy [52 cases, 21.9%)] and had no diseases known to affect bone and mineral metabolism. The best correlation was found between urinary DPYRI and urinary TPYRI (r = 0.63, P= 0.0001), followed by urinary Crosslaps and urinary DPYRI (r = 0.47, p = 0.0001). Only weak but significant correlations between E₂ and urinary Crosslaps (r =−0.21, P < 0.0001) as well as serum E₂ and serum osteocalcin (r =−0.16, P= 0.0007), were observed. Of the 237 women 53% suffered from a severe E₂ deficiency (E₂ < 10.0 ng/liter). In these patients, urinary Crosslaps (+48%) and serum osteocalcin (+22%) were significantly higher (P < 0.0001) compared with those patients with E₂ levels > 10 ng/liter. Women with E₂ levels >10 ng/liter were further subdivided into those with and without sex hormone replacement therapy, whereby no statistical differences in any of the biochemical markers could be observed between these groups. We could clearly demonstrate that in postmenopausal women suffering from severe E₂ deficiency (E₂ < 10 ng/liter), urinary Crosslaps and serum osteocalcin are significantly increased, indicating in principle a clear correlation between E₂ deficiency and these markers of bone turnover. Received: 3 February 1997 / Accepted: 15 October 1997     

Does Weight Loss Improve Incontinence in Moderately Obese Women?

The aim of this study was to evaluate the effect of weight reduction on urinary incontinence in moderately obese women. This prospective cohort study enrolled moderately obese women experiencing four or more incontinence episodes per week. BMI and a 7-day urinary diary were collected at baseline and on the completion of weight reduction. The study included 10 women with a mean (tSD) baseline BMI of 38.3 (t10.1) kg/m² and 13 (t10) incontinent episodes per week. Participants had a mean BMI reduction of 5.3 (t6.2) kg/m² (P<0.03). Among women achieving a weight loss of ≥5%, 6/6 had ≥50% reduction in incontinence frequency compared to 1 in 4 women with <5% weight loss (P<0.03). Incontinence episodes decreased to 8 (t10) per week following weight reduction (P<0.07). The study demonstrated an association between weight reduction and improved urinary incontinence. Weight reduction should be considered for moderately obese women as part of non-surgical therapy for incontinence.     

Effects of Age on Serum Dehydroepiandrosterone Sulfate, IGF-I, and IL-6 Levels in Women

Data from animal and in vitro studies suggest that the growth-promoting effects of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) may be mediated by stimulation of insulin-like growth factor-I (IGF-I) and/or inhibition of interleukin 6 (IL-6), a cytokine mediator of bone resorption. This study tests the hypotheses that there are effects of age on serum DHEAS, IGF-I, and IL-6 levels, and that levels of IGF-I and IL-6 are related to DHEAS levels. The study included 102 women: 27 premenopausal and 75 postmenopausal, including 35 postmenopausal women with osteoporosis, as defined by bone mineral density scores by dual X-ray energy absorptiometry. DHEAS levels decreased significantly with age (r =−0.52, P < 0.0001) and IGF-I levels decreased significantly with age (r =−0.49, P < 0.0001). IL-6 levels increased significantly with age (r = 0.36, P= 0.008). IGF-I was positively correlated to DHEAS levels (r = 0.43, P < 0.0001, n = 102) and IL-6 levels were negatively correlated to DHEAS levels (r =−0.32, P= 0.021, n = 54). Levels of DHEAS and IGF-I were correlated with T scores of the spine and some hip sites. In a multiple variable model to predict DHEAS, age was an important predictor (P < 0.001), but osteoporosis status, IGF-I, and IL-6 were not. The median DHEAS level was lower in the postmenopausal osteoporotic women (67 μg/dl, n = 35) than in the nonosteoporotic postmenopausal women (106.3 μg/dl, n = 40, P= 0.03), but this was not significant after correction for age. Age accounted for 32% of the variance in DHEAS levels. In summary, DHEAS levels decreased with age and had a positive association with IGF-I levels and a negative association with IL-6 levels. DHEA deficiency may contribute to age-related bone loss through anabolic (IGF-I) and anti-osteolytic (IL-6) mechanisms. Received: 28 June 1999 / Accepted: 11 January 2000     

Total Body Bone Measurements in Spinal Osteoporosis by Dual-Energy X-Ray Absorptiometry

Changes in total body bone mineral content (BMC_TB) and density (BMD_TB), and the T-score of BMC_TB and (BMD_TB) were evaluated in relation to the number of vertebral fractures in women with postmenopausal osteoporosis for the purpose of defining deviations in these parameters that could be predictive of the occurrence of vertebral fracture. The study group consisted of 62 women diagnosed with postmenopausal osteoporosis. All of them had two or more spinal fractures. Regression analysis of the number of fractures against each parameter studied indicated that the following were predictive of the risk of fracture: a reduction of −0.5 in the T-score of both BMC_TB and BMD_TB (P < 0.0001) and a loss of about 135 g of BMC_TB or 0.058 g/cm² of BMD_TB (P < 0.0001). The fact that such changes were found during the follow-up of women with osteoporosis highlights the importance of bone mass measurements during follow-up. Received: 9 July 1996 / Accepted: 3 January 1997     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

High Bone Turnover is Associated with Low Bone Mass and Spinal Fracture in Postmenopausal Women

A group of 366 healthy, white postmenopausal women, aged 50–81 years, mean age 66 years, were selected from the screened population of Scandinavians who were part of a multicenter study of the efficacy of tiludronate, a new bisphosphonate, in established postmenopausal osteoporosis. Eighty-eight women had a lumbar spine bone mineral density (BMD) above 0.860 g/cm², and 278 women had a BMD below 0.860 g/cm². Spinal fracture was diagnosed from lateral spine X-ray studies and defined as at least 20% height reduction (wedge, compression, or endplate fracture) in at least one vertebra (T4–L4). Bone resorption was assessed by measurement of the urinary excretion of type I collagen degradation products by the CrossLaps™ enzyme-linked immunoassay (ELISA). Bone formation was assessed by ELISA measurement of the N-terminal-mid-fragment as well as the intact serum osteocalcin (OC_N-MID), thus omitting the influence of the instability of osteocalcin caused by the labile 6 amino acid C-terminal sequence. The women were divided into groups with high or low bone turnover according to the concentrations of urinary CrossLaps™ or OC_N-MID. Women in the quartiles with the highest concentrations of CrossLaps [519 ± 119 μg/mmol (SD)] or OC_N-MID [44.6 ± 7.5 ng/ml (SD)] had 10–16% lower spinal BMD compared with women in the lowest quartiles (CrossLaps 170 ± 48 μg/mmol (SD), and OC_N-MID [22.1 ± 3.0 ng/ml (SD)] (P < 0.0004). The prevalences of spinal fracture were 25 to 29% in the lowest quartiles, whereas the prevalences in the highest quartiles were almost double—53–54% (P < 0.006). If the women were subgrouped according to spinal BMD and prevalence of spinal fracture, corresponding results were found. Women with a BMD less than 0.860 g/cm², without or with spinal fracture (n = 136 and n = 142), had 36–43% higher concentration of CrossLaps (P= 0.0001) and 11–15% higher concentration of OC_N-MID (P < 0.02), as compared with women with a BMD above 0.860 g/cm² and no spinal fracture (n = 84). In conclusion, the results indicate a strong association among high bone turnover, low bone mass, and prevalence of spinal fracture, which supports the theory that high bone turnover is a risk factor for spinal fracture and osteoporosis. Received: 29 February 1996 / Accepted: 9 August 1996     

Cortical Bone Resorption in Osteoporosis

A study was made of 110 women: 35 healthy premenopausal, 40 healthy postmenopausal, and 35 women diagnosed as having postmenopausal osteoporosis. The postmenopausal women had similar ages and years since menopause (YSM). In all of the women, total bone mass was evaluated by dual-energy X-ray absorptiometry and metacarpal morphometry was evaluated by radiogrammetry on the second metacarpal of the nondominant hand, performed by computed radiography. An external metacarpal diameter of ≥7.4 mm was required as proof of having developed an adequate peak bone mass. The endosteal diameter, which is indicative of bone resorption in both groups of postmenopausal women, obtained in the postmenopausal groups was subtracted from the endosteal diameter obtained in the premenopausal group and the resulting figure was divided by the years since menopause to calculate the rate of cortical bone resorption/year for each group. The endosteal diameters values differed in the three groups studied (P < 0.0001): 3.2 ± 0.7 mm in the healthy premenopausal women; 3.9 ± 0.6 mm in the healthy postmenopausal women; and 4.7 ± 0.5 mm in the osteoporotic postmenopausal women. The rate of cortical bone resorption was 0.068 ± 0.002 mm/YSM (years since menopause) in the osteoporotic postmenopausal women and 0.033 ± 0.003 mm/YSM in the healthy postmenopausal women (P < 0.0001). These figures reflect the importance of bone resorption, as opposed to deficient bone formation, as a cause of osteoporosis. Received: 27 January 1995 / Accepted: 21 August 1996     

Influence of Grip Strength on Metacarpal Bone Mineral Density in Postmenopausal Japanese Women: A Cross-Sectional Study

Most published studies on the role of muscle strength in the maintenance of bone mineral density (BMD) focused on the relationship between specific muscle groups and adjacent bones, mostly in young and premenopausal women. This study examined the influence of grip strength on BMD of the metacarpal index in postmenopausal Japanese women. Subjects included 1168 postmenopausal women aged 40–70 years. BMD measurement was done with computed X-ray densitometry (CXD) by analyzing X-ray films of the right second metacarpal index. Grip strength was measured in both the dominant and nondominant hands using a squeeze dynamometer. Grip strength (r = 0.2474; P= 0.0001) and age (r =−0.5443; P= 0.0001) significantly correlated positively and negatively, respectively, with BMD. Physical activity (r = 0.1318; P= 0.0001) also correlated positively with BMD. Breastfeeding (r =−0.1658; P= 0.0001), however, correlated negatively with BMD. Subjects with a history of regular physical activity had higher grip strengths and BMD, than those with no physical activity. Adjustment for age, physical activity, calcium intake, BMI, breastfeeding, testing site, and menopausal type indicated a significant (P for trend = 0.0013) positive association of grip strength with BMD. Subjects with stronger grip strengths had a decreased risk for low BMD. Received: 24 February 1998 / Accepted: 7 August 1998     

Effect of Lead on Bone Development and Bone Mass: A Morphometric,Densitometric, and Histomorphometric Study in Growing Rats

The effect of exposure to lead on the longitudinal development of bone and on bone mass was studied in rats. A group of 35, 50-day-old female Wistar rats was divided into a control group of 15 rats and an experimental group of 20 rats fed a diet supplemented with 17 mg of lead acetate per kg feed for 50 days. Total body bone densitometry (TBBMC) was performed the day before ending the 50-day experiment. On day 50, all rats were killed and their right femur and 5th lumbar vertebra were dissected. The bones were cleaned of soft tissue and femoral length and vertebral length were measured with a caliper and all bones were weighed on a precision scale. Final body weight (P < 0.05), TBBMC (P < 0.005), and femur weight (P < 0.005) were significantly lower in the control group. Femur length did not differ between groups, but the length of the 5th lumbar vertebra was greater in the control group (P < 0.05). Histomorphometry of the femur showed that Cn-BV/TV, Tb-N, Tb-Th were lower (P < 0.05 in all) and Tb-Sp was higher (P < 0.05) in the group given the lead-supplemented diet. These findings suggested lead-induced inhibition of axial bone development and a histomorphometric decrease in bone mass, produced mainly by enhanced resorption, and a densitometric increase in bone mass, produced by lead accumulation in bone. Received: 12 February 1996 / Accepted: 15 July 1996     

Influence of body composition on quantitative ultrasound parameters of the os calcis in a population-based sample of pre- and postmenopausal women

Body mass is known to be related to measures of bone mineral density (BMD) as well as to parameters of quantitative ultrasound (US). To examine the effect of the body compartment's fat mass and lean body mass on quantitative ultrasonic bone parameters, data from a sample of 3241 German women were analyzed. Anthropometric measures, including skinfold thickness, were obtained from standardized measurements, and fat and lean body mass were derived from classical regression formulas based on skinfold measurements. Ultrasonic bone measurements were performed on the right os calcis, and speed of sound (SOS) and broadband ultrasound attenuation (BUA) were determined. Women were grouped into pre- and postmenopausal status; postmenopausal women were further stratified into ever and never hormone-replacement user. Correlation analysis indicated lean body mass to be stronger correlated with BUA than fat mass in both pre- (r = 0.23; P= 0.0001) and postmenopausal women with (r = 0.19; P= 0.0001) and without hormone replacement therapy (HRT) (r = 0.26; p = 0.0001). SOS demonstrated very small or no associations with body mass or its components. Multiple linear regression models were used to describe the relationship among body weight, fat mass, and lean body mass on BUA after adjustment for confounding variables. Both in pre- and postmenopausal women lean body mass was more strongly related to BUA than fat mass. However, body mass measures explained only small amounts of the overall variance in BUA (R²= 1–3% in premenopausal women; R²= 1% postmenopausal with HRT; R²= 4–5% in postmenopausal women without HRT). In conclusion, the strong influence of body mass and its components previously reported for BMD was not observed for quantitative ultrasonic bone parameters. Received: 5 January 1999 / Accepted: 1 July 1999     

Determinants of the Need for Intensive Care and Prolonged Mechanical Ventilation in Patients Undergoing Bariatric Surgery

Background: Bariatric surgery at the upper extremes of weight can be associated with serious postoperative complications. In many cases, these complications will require the availability of critical care resources. The purpose of this study is to examine factors that increase the likelihood for prolonged postoperative intensive care unit (ICU) and extended mechanical ventilation (MV) >24 hours. Methods: A retrospective chart review was conducted of all patients undergoing bariatric surgery over a 7-year period at a tertiary care academic institution. There were 250 total patients undergoing either vertical banded gastroplasty (n=15) or Roux-en-Y gastric bypass (n=235). Age, Gender, BMI, pulmonary co-morbidity, revisional surgery (previous bariatric operations), and need for reoperation for suspected intra-abdominal complications were examined by univariate and multivariate analyses. Results: Mean age was 43.6±10.6 years and mean BMI 56±10.6 kg/m². Pulmonary co-morbidity was present in 123/250 patients (49%), 42/250 (17%) had revisional surgery, and 21/250 (8%) required reoperation. ICU care was required in 60 patients (24%). By univariate analysis, age >50 yrs (P =0.047), male gender (P =0.038), and need for reoperation (P <0.001) were associated with need for ICU. By multivariate analysis, BMI >60 kg/m², odds ratio (OR) 2.25, 95% confidence Interval (CI) 1.11-4.60, P =0.04, and need for reoperation, OR 39.8, 95% CI 10.41-264.7, P <0.0001, were associated with need for ICU. MV >24 hrs was required in 44 patients (18%). By univariate analysis, BMI >60 kg/m² (P =0.013), pulmonary co-morbidiy (P =0.014), male gender (P =0.029), and reoperation (P <0.0001) were associated with need for MV. By multivariate analysis, BMI >60 kg/m², OR 3.1, 95% CI 1.44-7.13, P =0.005, and need for reoperation, OR 22.3, 95% CI 7.4-79.2, P <0.0001, were associated with need for MV. Conclusions: Patients who are male, older (>50 yrs), heavier (BMI >60 kg/m²), and who have complications requiring reoperation will likely need intensive care. Additionally, males, heavier patients (BMI >60 kg/m²), pulmonary co-morbidity, and need for reoperation may warrant need for extended MV. Surgeons and hospitals should consider this when planning resources for bariatric surgery programs.     

Ultrasound and X-ray-Based Bone Densitometry in Patients with Anorexia Nervosa

In 20 patients (mean age 23 ± 5 years) with anorexia nervosa (AN), bone mass was evaluated by broadband ultrasound attenuation (BUA) of the calcaneus, peripheral quantitative computed tomography (pQCT) of the distal radius, and dual X-ray absorptiometry (DXA) of the lumbar spine and the hip. Compared with 20 age- and sex- matched healthy controls, patients with AN showed marked osteopenia at all measuring sites. Values of BUA (33.0 ± 9dB/MHz vs. 51.0 ± 5.7 dB/MHz; P < 0.0001) and of BMD of all regions of the hip (e.g., femoral neck: 0.71 ± 0.13 g/cm² versus 0.89 ± 0.07 g/cm²; P < 0.001), lumbar spine (0.82 ± 0.15 g/cm² versus 1.24 ± 0.06 g/cm²; P < 0.003) and total BMD of the peripheral radius (303.2 ± 75 g/cm³ versus 369.4 ± 53.2 g/cm³, P < 0.001) were significantly reduced. Calculating a Z-score we found the most prominent differences between AN and controls by BUA of the calcaneus (−3.2 ± 1.6), followed by DXA at the lumbar spine (−2.9 ± 2.2) and the hip (femoral neck −2.1 ± 1.7) and by pQCT at the distal radius (total BMD −1.2 ± 2.0). There were highly significant correlations between BUA of the calcaneus and BMD of the femoral neck (r = 0.78, P < 0.0001) and lumbar spine (r = 0.75, P < 0.0001) as well as between BMD values of the femoral neck and lumbar spine (r = 0.95; P < 0.0001). In addition, there were significant correlations (P < 0.001) between body mass index (BMI) and the three different measuring sites and between the duration of the disease and BUA (r = 0.5, P < 0.05). Our data suggest that BUA of the calcaneus is a valuable tool in the management of osteoporosis. Being a fast, radiation-free investigation method of good acceptance, it may be well suited for an assessment of the skeletal status in patients with AN. Received: 14 October 1998 / Accepted: 10 December 1999     

Calcidiol and PTH Levels in Women Attending an Osteoporosis Program

We performed a retrospective study of 237 patients attending a specialty osteoporosis practice. Secondary causes for reduced bone mineral density (BMD) were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age was 56 ± 13.8 years (mean ± SD). BMD was measured by dual-energy X-ray absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour urinary calcium were measured, and serum and urine protein (SPEP and UPEP) electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in iPTH levels. Among the osteoporotic patients (T score <−2.5 SD), 17% had 25(OH)D levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (−2.5 < T < −1.0 SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score ≤−1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D levels were inversely related to high iPTH values (r = 0.30, P < 0.0001). Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65 pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in 4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of 25(OH)D levels is recommended in the evaluation of secondary causes for reduced BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25 ng/ml, the level required to prevent increments in iPTH levels. Received: 9 February 1998 / Accepted: 1 October 1998     

Imaging Ultrasonometry of the Calcaneus: Dependence on Calcaneal Area

The purpose of this study was (1) to investigate the dependence of broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured in a circular region of interest (ROI) having a fixed size on calcaneal area and (2) to examine whether the normalization of ultrasonic variables for the area of the calcaneus provides better differentiation of diseased subjects from healthy individuals. Ultrasound variables were estimated in 169 healthy postmenopausal women (mean age 66.5 years, range 42–87 years) and 39 women with vertebral fractures (mean age 72.9 years, range 51–86 years). A minimum attenuation ROI, 15 mm in diameter, with a commercial imaging ultrasonometer was used. Significant relationships were found between both ultrasonic variables and calcaneal area (r²= 0.06, P < 0.001 for BUA, r²= 0.12, P < 0.0001 for SOS). Normalization of ultrasound variables (BUAn and SOSn) was based on the regression equations of the relationships among BUA, SOS, and calcaneal area. In a precision study, nine women were examined five times each to determine the errors arising from both the repositioning of the foot and selection of the calcaneal area. The reproducibility errors of BUA, SOS, BUAn, SOSn, and area were 0.87%, 0.20%, 1.07%, 0.27%, and 3.72%, respectively. Significant differences were found between the areas under the ROC curve for BUAn and BUA (area under the curve = 0.93 for BUAn versus 0.90 for BUA, P= 0.003) as well as for SOSn and SOS (area under the curve = 0.85 for SOSn versus 0.79 for SOS, P= 0.003). Normalization of ultrasound variables for calcaneal area improves the discrimination of clinical studies. Received: 7 June 1999 / Accepted: 18 January 2000