Weight and Body Mass Index at Menarche are Associated with Premenopausal Bone Mass

Adolescence is a critical time for skeletal growth and mineralization. Exposure to protective or detrimental factors during this period may influence peak bone mass attainment and subsequent development of osteoporosis. In order to evaluate the association of body size during adolescence with subsequent adult bone mass, we conducted a follow-up study of a community-based cohort of girls who participated in a growth and sexual maturation study 30 years ago. Data from the original study included age at menarche, height at menarche and weight at menarche. Follow-up evaluation of 119 subjects, now premenopausal women ages 40–45 years, included bone mineral density (BMD) measurements of the total body, lumbar spine, femoral neck, total hip, and ultradistal radius by dual-energy X-ray absorptiometry. After adjustment for current adult weight and other factors related to bone mass, weight at menarche was found to be positively associated with subsequent adult BMD. Similarly, body mass index (BMI) at menarche was positively associated with adult BMD. In contrast, age at menarche was not found to predict adult BMD. When the subjects were divided into quartiles based on their BMI at menarche, subjects in the lowest quartile of BMI at menarche had adult mean BMD that was 8–15% lower at the measured sites compared with subjects in the highest quartile of BMI at menarche. In conclusion, low body weight and low BMI at menarche appear to be significant predictors of reduced bone mass in healthy premenopausal women ages 40–45 years. Received: 15 August 2000 / Accepted: 2 January 2001     

A Clinical Prediction Rule to Identify Premenopausal Women with Low Bone Mass

Identifying premenopausal women at risk for osteoporosis and related fractures is a potentially important way to reduce the burden of illness from this disease as low peak bone mass is a risk factor for postmenopausal osteoporosis. We examined predictors of ‘low’ peak bone mass in 668 healthy, pre-menopausal, Caucasian women ages 18–35 years. Predictors of bone mass were assessed using a detailed, standardized interview. Bone mass was assessed using two measures: dual-energy X-ray absorptiometry (DXA) at the femoral neck and lumbar spine, and quantitative ultrasound (QUS) of the heel, which evaluates stiffness, speed of sound (SOS) and broadband ultrasound attenuation (BUA). Bone mass was considered ‘low’ if the corresponding Z-score was <–1.00 (DXA values, stiffness) or if values were in the lowest quintile (BUA, SOS). Using multivariate logistic regression modeling, predictors of low bone mass based on QUS, DXA or both were determined. The mean age of the cohort was 27.3 years. Independent predictors of low bone mass by both DXA and QUS were: low body weight, menarche at age 15 years or later and physical inactivity as an adolescent. Individuals with all three risk factors had a 92% chance of having low bone mass using both techniques. This suggests that a simple risk factor assessment can identify most young women with low peak bone mass. Early intervention in this group of women may reduce the risk for osteoporosis in later life. Received: 2 June 2000 / Accepted: 20 November 2001     

Allogeneic Bone Marrow Transplantation is Associated with a Preferential Femoral Neck Bone Loss

Osteoporosis is a major complication of organ transplantation. Little is known about the risk of developing osteoporosis in bone marrow transplant (BMT) recipients. We studied early and late changes in bone mineral density (BMD), as well as biochemical markers of bone remodeling, in patients at the time of allogeneic BMT (alloBMT) and up to 13 years thereafter. In a cross-sectional study, 102 patients (40 women, 62 men, mean age ± SEM, 38.9 ± 1.6 years) were segregated into a first group (A, n= 48) and evaluated before or during the first weeks (mean ± SD 0.3 ± 0.1 month, range –0.5 to 3 months) following alloBMT, and a second group (B, n= 54) studied 60.1 ± 5.6 months (range 6–156 months) following alloBMT. Lumbar spine (LS) BMD was similar in groups A and B and was within normal limits. In contrast, femoral neck (FN) Z- and T-scores were significantly decreased in group B compared with group A (–0.68 ± 0.14 vs –0.03 ± 0.14 SD and –0.84 ± 0.14 vs –0.22 ± 0.14 SD, respectively; p≤0.002). Osteopenia (T-score between –1 and –2.5 SD) was present in 35% of group A and 43% of group B patients (NS). Osteoporosis (T-score <–2.5 SD) was detected in 7% of group B patients, but in none of those in group A (p= 0.05). In a longitudinal study, 56 subjects were evaluated at the time of alloBMT, and 33 and 23 were studied 6 or 12 months later, respectively (13 women, 20 men, 37.5 ± 1.6 years). All were treated with supplements of calcium and vitamin D. Amenorrheic women received hormone replacement therapy (HRT). Three-monthly pamidronate infusions were given to 15 men and 10 non-amenorrheic women who were osteopenic/osteoporotic or had elevated baseline bone turnover markers. Mean baseline LS and FN Z- and T-scores were within normal range. Six months after BMT, FN BMD decreased by 4.2 ± 0.7% (p<0.001), and whole body BMD and bone mineral content by 1.5 ± 0.4% and 3.1 ± 0.6%, respectively (p≤0.0001). Twelve months after the graft, there was no further significant bone loss and only FN BMD decrease remained significantly different compared with baseline (–5.6 ± 1.1%, p≤0.0001). These results indicate that the risk of decreased BMD is higher for the femoral neck than the lumbar spine and whole body levels in patients with allogeneic bone marrow transplantation, and that bone loss occurs mainly during the first 6 months after the graft. Received: 9 February 2001 / Accepted: 23 May 2001     

Bone Mass Change During Methotrexate Treatment in Patients with Juvenile Rheumatoid Arthritis

Thirty-two children affected by juvenile rheumatoid arthritis (JRA) were studied with serial measurements of bone mass for an average of 18 months, to evaluate the effects of long-term methotrexate (MTX) treatment on bone. Bone mineral density (BMD) was measured on lumbar spine and total body. During MTX therapy some increase in BMD was observed, though this was smaller than in a control group of healthy children. Axial (spine and trunk) and appendicular (upper and lower limbs) BMD showed similar increases. BMD, either as an absolute value or as a percent variation from baseline, did not correlate with either MTX dose or length of therapy. In children treated also with corticosteroids, these drugs negatively influenced bone mass increase. The main determinant of absolute spine BMD value appeared to be weight, while height and lean mass seemed to be the determinants of total body BMD. Pubertal stage and disease activity significantly influenced the yearly change in BMD. In conclusion, our data suggest that long-term, low-dose therapy with MTX does not induce osteopenia in children with JRA. Received: 17 July 1998 / Accepted: 10 November 1998     

Anorexia Nervosa: Slow Regain of Bone Mass

In a retrospective study of women aged 18–30 years, aimed at assessing factors associated with peak bone mass (PBM), 13 of 239 study cases reported having had anorexia nervosa. The mean total femoral and lumbar bone mineral density (BMD) values were not significantly lower in women who had had anorexia than in the pooled group (mean Z-scores of –0.60 and –0.48). Cases with less than 6 years since the anorexia had on average a present weight 5.7 kg less than their pre-morbid weights, while cases with more than 6 years since the eating disorder had an average weight 22.5 kg above their pre-morbid weights. The cases who had not regained their weight had BMD values significantly lower than the pooled material (mean Z-scores –1.15 and –0.9 in the lumbar spine and total femur respectively). Those who had regained their weight had BMD values as predicted from their present anthropometric data, while those who had not regained their weight had BMD values that were substantially below that predicted from their present weight. Anorexia nervosa seems to be associated with a low BMD which is even lower than that which can be predicted from the weight loss alone. This suggests that weight loss and other factors, such as menstrual dysfunction and estrogen deficiency, are independent and thus additive causes of bone loss in anorexia nervosa. Recovery of BMD seems slow, but the BMD may become as predicted from the anthropometric data after restoration of body weight and menses. The potential for recovery of BMD seems intact for several years after menarche. Received: 19 May 1998 / Accepted: 7 July 1999     

Birth Weight as a Predictor of Adult Bone Mass in Postmenopausal Women: The Rancho Bernardo Study

Understanding the determinants of adult bone mass may help to identify women for prevention of osteoporosis. We postulated that birth weight would predict low adult bone mass in old age. Subjects were 305 postmenopausal Caucasian women (mean age 70 years). Bone mineral content (BMC) and bone mineral density (BMD) were measured at the wrist, forearm, hip and lumbar spine. Birth weight was assessed by self-report. Birth weight was positively correlated with BMC at the forearm (r= 0.15), hip (r= 0.12) and lumbar spine (r= 0.18), and the age-adjusted mean BMC increased significantly from the lowest to the highest birth weight tertile. Adjusting for adult weight diminished this association at the forearm and hip, but not at the spine. Adjustment for multiple other covariates, including height, did not materially change these associations. Adult weight and height were significantly correlated with birth weight (r= 0.19 and r= 0.24, respectively). Birth weight was not independently correlated with BMD. Birth weight was thus positively correlated with adult weight and BMC 70 years later. These findings suggest that low birth weight may be a marker for future low bone mass and that different mechanisms exist for establishing the adult bone envelope (estimated by BMC) versus its density (estimated by BMD). Received: 18 August 1999 / Accepted: 21 January 2000     

Bone Biomechanical Property Deterioration Due to Tobacco Smoke Exposure

Tobacco smoking has been implicated in the development of osteoporosis and early onset of menopause in women smokers. We measured various biomechanical properties of femurs and tibiae obtained from smoke-exposed and control mice to determine cigarette smoke influences on bone mass, structure, and strength. Growing female C57BL mice were exposed to sidestream cigarette smoke in a whole-body exposure chamber, set at 30 ± 2 mg smoke particulates/m³ for 4 hours/day and 5 days/week for 12 consecutive weeks. Elevated levels of urinary cotinine and pulmonary ethoxyresorufin deethylase activity in smoke-exposed mice confirmed their effective exposure to cigarette smoke. There were no differences in body weight and physical size (length, medial-lateral and anterior-posterior widths, midshaft cortical area and thickness) of femurs and tibiae between smoke-exposed and control mice. The femoral mid-shaft yield load, stiffness, yield stress, and modulus were, respectively 8%, 13%, 10%, and 14% lower (P < 0.05) in smoke-exposed compared to control mice. The ultimate load and stress in mid-shaft femurs showed decreasing trends (P < 0.1) in smoke-exposed mice. In the femoral neck, the ultimate load and stiffness were 9% and 12% lower (P < 0.05) in smoke-exposed mice, respectively. Further, the ash-to-dry bone weight ratio was smaller (∼6%, P < 0.05), and micro-computed tomographic scanning of distal femoral bone volume/total volume (%) and trabecular thickness showed decreasing trends in smoke-exposed mice compared to the control group. We conclude that exposure to tobacco smoke deteriorates some of the biomechanical properties of bone in growing female mice.     

Association of Physical Activity and Calcium Intake with the Maintenance of Bone Mass in Premenopausal Women

Altogether 92 initially 25- to 30-year-old women of 132 original subjects participated in this 4-year follow-up study, which evaluated the influence of physical activity and calcium intake on the bone mineral content (BMC) of premenopausal women. The subjects were originally selected for a cross-sectional study according to their level of physical activity (high PA⁺ and low PA^–) and calcium intake (high Ca⁺ and low Ca^–), and the original groups were maintained in this follow-up study. The mean loss of BMC (95% CI) in the pooled data was 1.5% (0.7% to 2.4%) at the femoral neck, 0.6% (–0.8% to 1.9%) at the trochanter and 6.0% (4.5% to 7.4%) at the distal radius during the 4-year follow-up. According to repeated measures analyses of covariance neither physical activity nor physical fitness at baseline was associated with the rate of bone loss from the proximal femur. High calcium intake and the maintenance of body weight were both associated with a lower rate of bone loss from the proximal femur and distal radius. In addition, a long duration of breast feeding was associated with a higher rate of bone loss from the distal radius. Received: 1 June 2001 / Accepted: 29 August 2001     

Premature Greying of the Hair Is Not Associated with Low Bone Mineral Density

In two recent case–control studies premature greying of the hair was associated with a lowering of bone mineral density (BMD) and osteopenia, suggesting that this might be a clinically useful risk marker for osteoporosis. We report a further re-examination of this proposal in 52 prematurely grey-haired women from East Yorkshire who responded to an advertisement inviting them for bone densitometry. Thirty-five had no clinical or drug history that could influence bone density. All were Caucasian with a mean age of 52.8 years. In the group as a whole the mean BMD values at the lumbar spine and femoral neck were no different from those of a young adult, but there was a trend toward a greater than average BMD than that of the local age-matched population (p= 0.097 and 0.218, respectively). Twenty women were premenopausal, with an average age of 45.3 years. Mean BMD values at the lumbar spine and femoral neck in this group were no different from those of young adults. There was, however, a trend toward a BMD greater than that of the local age-matched population at the femoral neck (p= 0.117). Fifteen women were postmenopausal with an average age of 62.9 years and an average age at menopause of 51.1 years. Mean BMD values at both the lumbar spine and femoral neck in this group were lower than those of young adults, but no different from those of the local age-matched population. In conclusion, our group of prematurely grey-haired women had average BMD for their age, and we are therefore unable to support the proposed clinical usefulness of premature greying as a risk marker for osteoporosis. Received: 1 December 1998 / Accepted: 11 March 1999     

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     

Exercise May Induce Reversible Low Bone Mass in Unloaded and High Bone Mass in Weight-Loaded Skeletal Regions

Exercise during growth and adolescence increases bone mineral density (BMD) in weight-loaded skeletal regions. The development of BMD in unloaded or minimally loaded regions during activity is unclear. We measured BMD in one unloaded, one partly loaded and one highly loaded skeletal region in 67 active soccer players, mean age 22.7 years (range 17–35 years), 128 former soccer players, mean age 54.0 years (range 19–85 years) and 138 controls, mean age 50.6 years (range 19–80 years). The active soccer players played at three different levels: premier league, 3rd league or 6th league. Duration of exercise in these three groups was 12, 8 and 6 h/week, respectively. BMD (g/cm²) was measured by dual-energy X-ray absorptiometry (DXA) in the upper part of the skull (the unloaded skeletal region), the arms (the partly loaded region) and the femoral neck (the maximal loaded region). Data are presented as mean ± SD. Active soccer players had 10.3 ± 10.4% lower BMD in the upper part of the skull (p<0.001), 1.4 ± 6.3% higher BMD in the arm (NS) and 12.7 ± 9.8% higher BMD in the femoral neck (p<0.001) compared with age- and gender-matched controls. All three levels of soccer players demonstrated, independent of activity level, the same discrepancies in BMD compared with controls. Former soccer players had lower BMD in the upper part of the skull until age 70 years and higher BMD in the femoral neck until age 50 years compared with controls. The BMD of the arm was not different in former soccer players compared with controls. In summary, active soccer players had lower BMD in the unloaded skeletal region, no difference in BMD in the partly loaded region and higher BMD in the weight-loaded region compared with controls. The discrepancies compared with controls diminished with age so that no differences were found in BMD after age 70 years. In conclusion, unloaded and weight-loaded skeletal regions may respond differently to increased and decreased physical activity. Received: 15 January 2001 / Accepted: 31 May 2001     

The Vitamin D Receptor Start Codon Polymorphism (Fok1) and Bone Mineral Density in Premenopausal Women in Taiwan

The vitamin D receptor gene (VDRG) polymorphism as a factor of bone turnover rate or bone mineral density (BMD) is a controversial issue, especially in different ethnic populations. In addition to intron 8 (Bsm1, Taq1) and exon 9 (Apa1), VDRG polymorphism is present at its translation initiation site on exon 2. The VDRG has two translation initiation sites. The first shows a thymine/cytosine polymorphism and can be detected by restriction fragment length polymorphism (RFLP) using the endonuclease Fok1. This start codon polymorphism (SCP) of the VDRG was detected by polymerase chain reaction and then by RFLP with Fok1. While the f allele was assigned for the presence of the restriction site, the F allele was assigned for the absence of the restriction site, and the encoded vitamin D receptor is shorter by three amino acids. We examined the association between this SCP of the VDRG and bone turnover as well as BMD in 101 premenopausal Taiwanese women aged 40–53 years. Total body bone mineral content and BMD of proximal femur and lumbar spine were measured by dual-energy X-ray absorptiometry. We found a prevalence of 39.6% for the f allele of the VDRG. The frequencies of FF, Ff and ff genotypes were 35.6%, 49.5% and 14.9%, respectively. There was no statistically significant difference in BMD at any site or bone turnover markers among the three Fok1 genotypes (FF, Ff and ff). The SCP is independent of Bsm1, Apa1 or Taq1 polymorphisms of the VDRG at intron 8 and exon 9. In conclusion, the SCP polymorphism detected by endonuclease Fok1 does not significantly influence BMD or bone turnover in premenopausal women in Taiwan. Received: 7 July 1998 / Accepted: 10 November 1998     

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     

Long-Term Follow-up of Bone Mass after Orthotopic Liver Transplantation: Effect of Steroid Withdrawal from the Immunosuppressive Regimen

Glucocorticoids have been suggested to play a major role in transplantation-related osteopenia. In this study we assess the long-term changes and the effect of steroid withdrawal from the standard immunosuppressive regimen on bone mineral density (BMD) after orthotopic liver transplantation (OLT). Sixty-nine non-osteoporotic patients (20 women, 49 men), aged 48 ± 9.5 years (mean ± SD), and with a follow-up of 58.3 ± 23.2 months (range 24–121 months) were studied. Immunosuppressive treatment consisted of prednisone, cyclosporin A and azathioprine. In 41 patients (group A), prednisone was tapered and withdrawn after 36.2 ± 19.3 months (range 13–79 months), whereas in 28 patients (group B) prednisone was maintained. BMD in the spine (L1–L4) was serially measured by dual-energy X-ray absorptiometry (Hologic QDR 1000w) at baseline, before steroid withdrawal and at the end of study. Age- and sex-matched Z-scores of BMD were calculated. No differences were found in age, body mass index, time since OLT, or baseline BMD between the two groups. BMD had significantly increased in both groups at the end of follow-up period (group A, +8.1 ± 8.7%; group B, +3.2 ± 8.0%, p<0.05). However, the Z-score was significantly higher in group A than in group B at the end of study (–0.44 ± 1.05 vs –0.99 ± 0.77; p<0.05). BMD recovery was lower in pre-OLT biliary cirrhosis patients. Bone mass improvement was independent of the time since OLT in both groups, and of the time of steroid withdrawal in group A. Our data confirm that steroid withdrawal accelerates the recovery of bone mass in patients who have undergone a successful liver transplantation. Received: 17 April 2001 / Accepted: 1 August 2001     

Suitability of the T-score for Establishing Bone Mineral Density Categories

The use of different reference ranges may give rise to different T-score values for the same bone mineral density (BMD) value. This study was designed to quantify the differences in the classification of a particular population on the basis of normal ranges obtained from other reference databases. The T-scores obtained in a sample of 148 women by applying the Spanish normal range were compared with the normal range obtained in NHANES III for femoral neck. Significant differences were found when T-scores were compared, but there were no differences in categorizations using the WHO criteria. The application of these reference ranges to a female population aged older than 45 years with known BMD showed significant differences in classification. In conclusion, the T-score can vary according to the normal range used as reference, but it has little influence on the categorization of individual patients. However, it may be important when applied to a general population. Received: 17 November 1999 / Accepted: 29 October 1999     

Prevalence of Reduced Bone Mineral Density in Patients with Anti-neutrophil Cytoplasmic Antibody Associated Vasculitis and the Role of Immunosuppressive Therapy: A Cross-Sectional Study

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a relapsing-remitting disease, which is treated with corticosteroids (CS) in combination with cyclophosphamide. One of the major side-effects of this treatment is osteoporosis, which may result in the increased occurrence of fractures. In the present study we measured the prevalence of reduced bone mineral density (BMD) in a cross-sectional cohort of patients and correlated BMD findings with cumulative doses of CS and/or cyclophosphamide. BMD was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine, radius and proximal femur between January 1998 and December 1999. Cumulative doses of CS and cyclophosphamide were calculated by chart review. Ninety-nine consecutive patients (48 men, 51 women) aged 55 ± 16 years (mean ± SD) were studied 50 months (median; range 0–400 months) after a diagnosis of ANCA-associated vasculitis had been made. Sixty-nine patients were treated with 10.7 g (median cumulative dose; range 0.4–67.2g) of CS, and 88 patients were treated with 34.1 g (median cumulative dose; range 0.8–324.3g) of cyclophosphamide. Fifty-seven percent of the patients had osteopenia (T-score: –1 to –2.5 SD), and 21% had osteoporosis (T-score: <−2.5 SD) at least at one site. Thirty-four of 37 (92%) postmenopausal women, 9 of 14 (64%) premenopausal women, and 34 of 48 (71%) men had either osteopenia or osteoporosis. The mean age- and sex-adjusted BMD (Z-score) of the proximal femur in men was found to be significantly lower than zero. Cumulative dose of CS therapy showed an inverse relation with Z-scores at the lumbar spine (p= 0.035) and proximal femur (p = 0.011). Cumulative dose of cyclophosphamide was not correlated with Z-scores. Osteopenia and osteoporosis are thus frequently observed in patients with ANCA-associated vasculities. However, only in men is the mean Z-score significantly lower than zero. Cumulative dose of CS therapy is significantly associated with bone loss at the spine and femur. Received: 26 March 2001 / Accepted: 1 August 2001     

Effects of Cigarette-Smoking on Bone Mass as Assessed by Dual-Energy X-ray Absorptiometry and Ultrasound

In order to elucidate the influence of nicotine smoking on bone mass in elderly women, bone mass was cross-sectionally assessed by dual energy X-ray absorptiometry (DXA) in total body, hip and lumbar spine, as well as with ultrasound of calcaneus and phalanges of the hand. Subjects were 1,042, 75-year old women, recruited on a population basis (Osteoporosis Prospective Risk Assessment (OPRA) study). We found bone mineral density (BMD) to be lower in hip (0.71 vs. 0.76 g/cm², p<0.0001 for femoral neck) and total body (0.96 vs. 1.02 g/cm², p<0.0001) in current smokers compared to never-smokers. There was no difference in BMD of the lumbar spine between current smokers and never-smokers. Bone mass as assessed by ultrasound of the calcaneus was lower for speed of sound (p<0.01), broadband ultrasound attenuation (p<0.0001) and stiffness (p<0.0001) in current smokers than in never-smokers. No differences were found for ultrasound measurements of the phalanges between smokers and never-smokers. Also, weight and current physical activity as assessed by a questionnaire differed significantly between current smokers and never-smokers.  There was no evident difference between former smokers and never-smokers in any of the skeletal regions assessed by DXA or ultrasound.  After correcting for differences in weight and physical activity, current smokers had lower BMD in all hip sites (p<0.05) and total body (p<0.01) compared to never-smokers. Ultrasound and BMD spine did not differ between these two groups after correction for weight and physical activity.  We conclude that nicotine smoking has a negative influence on bone mass independent of differences in weight and physical activity. This difference is detected by DXA but not by ultrasound measurements of the calcaneus or the phalanges. The present data are encouraging since no bone mass differences were found between former and never-smokers. Received: 29 March 2002 / Accepted: 2 July 2002     

Factors Related to Variation in Premenopausal Bone Mineral Status: A Health Promotion Approach

Bone loss prior to menopause may contribute to later risk of fracture due to osteoporosis. Women may be able to optimize premenopausal bone mass and/or prevent losses. Heredity, and possibly age at menarche (retrospectively determined), are unmodifiable risk factors and attention should therefore be directed to more amenable factors. Amenorrhea, low body weight, disordered eating, and smoking are modifiable risk factors. Vitamin D is not a factor for premenopausal women who receive incidental sun exposure and consume fortified foods, but supplementation should be considered for others, especially during the winter months. Protective factors include a higher body weight (especially due to increased muscularity), calcium supplementation, and purposeful load-bearing exercise. Positive effects of oral contraceptives are most apparent in women with menstrual irregularities. Reproductive history (parity), lactation, moderate intakes of alcohol and caffeine, and the appropriate treatment of endometriosis have no apparent effect on premenopausal bone. Received: 9 July 1998 / Accepted: 15 June 1999     

Comparison of Bone and Total Alkaline Phosphatase and Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Alendronate

Alendronate therapy in osteoporotic women decreases bone turnover and increases bone mineral density (BMD). Optimal patient management should include verification that each patient is responding to therapy. Markers of bone turnover and BMD have both been proposed for this purpose. We have investigated changes resulting from alendronate therapy with an enzyme immunoassay for bone alkaline phosphatase (BAP) and compared it with total alkaline phosphatase (TAP) and BMD of the lumbar spine, hip, and total body. Subjects were drawn from a multicenter randomized, placebo-controlled trial of alendronate in postmenopausal women with osteoporosis. BAP and TAP levels were measured at baseline and following 3, 6 and 12 months of therapy with either placebo (n= 180) or alendronate 10 mg/day (n= 134). All subjects also received 500 mg/day supplemental calcium. BMD was measured at baseline and following 3, 6, 12, 18, 24 and 36 months of therapy. To compare BAP, TAP and BMD at each site for identifying women that experienced a skeletal effect of alendronate, we calculated least significant change (LSC) values from the long-term intraindividual variability in each placebo-treated woman. Median levels of BAP decreased by 34%, 44% and 43% at 3, 6 and 12 months, respectively, in alendronate-treated women (p<0.0001 compared with baseline and with placebo). These changes were significantly greater (p<0.0001) than changes observed for TAP. Following 6 months of alendronate therapy, 90% of the women had experienced a decrease in BAP exceeding the LSC compared with only 71% for TAP. The greatest number of women similarly identified with BMD at any site (i.e. a gain in BMD exceeding the LSC) was 81% for spinal BMD at 36 months. All other sites were less than 70% at 36 months. Short-term changes in BAP and TAP were modestly associated with subsequent changes in BMD at all sites (Spearman’s rho −0.22 to −0.52, p<0.05). Compared with TAP and BMD, BAP testing rapidly and sensitively identified skeletal effects of alendronate thus enabling appropriate drug monitoring of osteoporotic women. Though BAP and TAP changes were modestly predictive of BMD changes, the value of the bone marker tests is their ability to detect rapidly a skeletal effect of therapy. Received: 19 May 2000 / Accepted: 31 October 2000     

Bone Mineral Density of the Lebanese Reference Population

We determined the bone mineral density (BMD) of normal Lebanese subjects and compared results with US/European reference data. The investigation was conducted at one center, and included 858 women and 165 men aged 20–79 years. Spine, femoral and radial BMD measurements were made using dual-energy X-ray absorptiometry. Age-related changes in BMD were similar in form to those of US/European reference data. However, BMD values of Lebanese were generally lower than US/European values. Spine BMD of Lebanese women was about 8% lower than US/European values between ages 20 and 59 years, and 5–6% lower for ages 60–79 years. Femoral neck BMD values for Lebanese women were 8% lower in the young adult years (age 20–39 years), but only 2–3% lower in the postmenopausal years, compared with US/European women. There were smaller postmenopausal decreases in femoral and radial BMD in Lebanese women compared with US/European women, which led to a convergence of BMD after age 70 years. The BMD of Lebanese men was 5–8% lower than US/European values throughout the age range (20–79 years). The effect of weight on BMD ranged from 0.2% to 0.4% per kilogram. Height was not significantly associated with BMD when both height and weight were entered in multiple regression analyses. The prevalence of osteoporosis appeared to be overestimated if the US/European reference data, rather than Lebanese reference data, were used to calculate T-scores. Received: 25 February 1999 / Accepted: 9 March 2000