Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset.

In order to determine whether growth hormone (GH) deficiency of childhood onset affects the adult bone mineral status, we assessed bone mineral content (BMC) by photon absorptiometry in 30 full-grown GH-deficient men (8 with isolated GH deficiency and 22 with multiple pituitary deficiencies; 28 previously treated with GH) and in 30 male controls matched for age (within 4 yr) and height (within 10 cm). Forearm BMC was measured by single photon absorptiometry just proximally of the distal one third of the nondominant forearm (PBMC-2 in arbitrary units and PBMC/bone width (BW) after normalization for bone width) and at a more distal site, close to the carpal joint (DBMC-2 and DBMC/BW). Lumbar BMC was measured by dual photon absorptiometry and reported as total BMC for L2-L4 (LBMC in g) and after normalization for projected area (LBMD in g/cm2). The patients had a significantly lower BMC, both at the forearm (P less than 0.0001) and at the lumbar spine (P less than 0.005): 35.7 +/- 1.0 vs. 50.0 +/- 1.6 and 36.9 +/- 1.2 vs. 52.8 +/- 1.9 (mean +/- SEM) for PBMC-2 and DBMC-2 in patients and controls, respectively; 1.36 +/- 0.03 vs. 1.70 +/- 0.04 and 1.07 +/- 0.03 vs. 1.35 +/- 0.04 for PBMC/BW and DBMC/BW; 34.00 +/- 1.08 vs. 42.02 +/- 1.27 g for LBMC and 0.886 +/- 0.016 vs. 0.976 +/- 0.018 g/cm2 for LBMD. Both the patients with isolated GH deficiency and the patients with multiple pituitary deficiencies were osteopenic when compared to their respective controls (P less than 0.01 to P less than 0.0001 for the patients with multiple deficiencies; statistical significance reached for PBMC-2, DBMC-2, and DBMC/BW only, P less than 0.05, in the small group of patients with isolated GH deficiency). For the patients (n = 19) who had at least three serial measurements over a period of 6 to 28 months, no decrease in BMC was detected. Our findings indicate that men with GH deficiency of childhood onset present with a low adult bone mass, despite prior GH substitution in most of these subjects. The observations of a more pronounced bone mineral deficit at the forearm (20-30% lower mean values, depending on the type of measurements) than at the lumbar spine (9-19%) and the findings of osteopenia in both the patients with isolated GH deficiency and multiple pituitary deficiencies, support the view that GH deficiency per se is responsible for part of the observed deficit.(ABSTRACT TRUNCATED AT 400 WORDS)     

Are adult patients with Laron syndrome osteopenic? A comparison between dual-energy X-ray absorptiometry and volumetric bone densities

Severe short stature resulting from a deficiency in IGF-I is a prominent feature of Laron syndrome (LS). Although low bone mineral density (BMD) has been noted in LS patients examined by dual energy x-ray absorptiometry (DEXA), this technique does not take volume into account and may therefore underestimate the true bone density in patients with small bones. The aim of the present study was to evaluate the BMD yielded by DEXA in our LS patients using estimated volumetric values. Volumetric density was calculated with the following formulas: bone mineral apparent density (BMAD) = bone mineral content (BMC)/(area)(3/2) for the lumbar spine and BMAD = BMC/area(2) for the femoral neck. The study sample included 12 patients (mean age, 43.9 yr; mean height, 123.7 cm). Findings were compared with 10 osteopenic subjects without developmental abnormalities (mean age, 56 yr; mean height, 164.8 cm) and 10 healthy control subjects matched for sex and age to the LS patients (mean height, 165.5 cm). BMAD in the LS group was 0.201 +/- 0.02 g/cm(3) at the lumbar spine and 0.201 +/- 0.04 g/cm(3) at the femoral neck; corresponding values for the osteopenic group were 0.130 +/- 0.01 and 0.140 +/- 0.01 g/cm(3), and for the controls, 0.178 +/- 0.03 and 0.192 +/- 0.02 g/cm(3). Although areal BMD was significantly lower in the LS and osteopenic subjects compared with controls (P < 0.02) at both the lumbar spine and femoral neck, BMAD was low (P < 0.01) in the osteopenic group only. In conclusion, DEXA does not seem to be a reliable measure of osteoporosis in patients with LS.     

The effects of oestrogen exposure on bone mass in male to female transsexuals

OBJECTIVE: The importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oestrogen exposure on BMD in transsexual men. DESIGN: Cross-sectional study of BMD in male to female transsexuals. PATIENTS: Subjects consisted of two groups of transsexual male dancers aged 16-34 years who did not receive transsexual operations (n = 28). Group 1 (n = 11) and group 2 (n = 17) had used oestrogen for 2 years or less and more than 2 years, respectively. Twenty-four healthy adult males served as controls. RESULTS: Signs of feminization were presented in both group 1 and group 2, with Tanner's stage II-III breast development. BMD at various sites were correlated only to body weight and not to smoking or milk consumption. After controlling for body weight, it was found that group 2 had significantly higher BMD at L2-4 than controls (1.22 +/- 0.03 vs. 1.14 +/- 0.03 g/cm2, P < 0.05) and group 1 (1.22 +/- 0.03 vs. 1.08 +/- 0.04 g/cm2, P < 0.05). BMD at femoral neck was also higher in group 2 compared to controls (1.10 +/- 0.03 vs. 1.01 +/- 0.03 g/cm2, P < 0.05) and group 1 (1.10 +/- 0.03 vs. 0.95 +/- 0.04 g/cm2, P < 0.05). Group 1 subjects had lower BMD compared to controls at femoral trochanter (0.70 +/- 0.04 vs. 0.83 +/- 0.03 g/cm2, P < 0.05) and total femur (0.96 +/- 0.05 vs. 1.07 +/- 0.03 g/cm2, P < 0.05). CONCLUSIONS: Long-term oestrogen exposure transsexual men result in an increase in bone mineral density despite signs of feminization. This suggests that oestrogen has positive effects on bone density in males. The finding of the trend towards reduced bone density in group 1 remains unexplained.     

The effects of race and body habitus on bone mineral density of the radius, hip, and spine in premenopausal women

The incidence of osteoporosis and fractures of the hip are diminished in blacks and in obese subjects. To determine whether bone mass is increased in them, bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual photon absorptiometry in 89 nonobese white and 51 nonobese black women, all of whom were within 30% of their ideal body weight and between the ages of 20 and 50 yr, and in 21 obese white women and 21 obese black women, all of whom weighed 30% on more than their ideal body weight and were in the same age range. The BMD of the mid radius was also measured by single photon absorptiometry. The mean BMD of the mid radius was higher in black than in white nonobese women [0.73 +/- 0.01 (+/- SE) vs. 0.70 +/- 0.01 g/cm2; P less than 0.01] and was not altered by obesity in either group. The mean BMD was higher in the black than in the white nonobese women at the lumbar spine (1.23 +/- 0.02 vs. 1.16 +/- 0.01 g/cm2; P less than 0.01), trochanter (0.78 +/- 0.02 vs. 0.72 +/- 0.01 g/cm2; P less than 0.01) and femoral neck (0.96 +/- 0.02 vs 0.90 +/- 0.02 g/cm2; P less than 0.02). The mean body weight was higher in the obese than in the nonobese white women (92 +/- 2 vs. 61 +/- 1 kg; P less than 0.001) and black women (94 +/- 3 vs. 63 +/- 1 kg; P less than 0.001). The mean BMD was higher in the obese than in the nonobese white women at the lumbar spine (1.24 +/- 0.03 g/cm2; P less than 0.05), trochanter (0.89 +/- 0.04; P less than 0.001), and femoral neck (0.99 +/- 0.03; P less than 0.01) and was higher in the obese than in the nonobese black women at the lumbar spine (1.33 +/- 0.03 g/cm2; P less tham 0.01), trochanter (0.88 +/- 0.04 g/cm2; P less than 0.05), and femoral neck (1.04 +/- 0.03 g/cm2; P less than 0.05). Multivariate regression analysis revealed positive correlations between body weight and BMD at each of the 3 weight-bearing sites, but not at the mid radius, in both the black women and white women.(ABSTRACT TRUNCATED AT 400 WORDS)     

Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma

The effect of subclinical hyperthyroidism on bone mineral density is controversial and could be significant in patients with differentiated thyroid carcinoma who receive suppressive doses of levothyroxine (LT4). To ascertain whether prolonged treatment with LT4 to suppress thyrotropin had a deleterious effect on bone mineral density and/or calcium metabolism in patients thyroidectomized for differentiated thyroid cancer we have performed a cross-sectional study in a group of 88 women (mean +/- SD age: 51 +/- 12 years) treated with LT4 after near-total thyroidectomy and in a control group of 88 healthy women (51 +/- 11 years) matched for body mass index and menopausal status. We determined calcium metabolism parameters, bone turnover marker N-telopeptide and bone mass density by dual-energy X-ray absorptiometry. No differences were found between patients and controls in calcium metabolism parameters or N-telopeptide except for PTH, which was significantly increased in controls. No differences were found between groups in bone mineral density in femoral neck (0.971 +/- 0.148 gr/cm(2) vs 0.956 +/- 0.130 gr/cm(2) in patients and controls respectively, P = 0.5). In lumbar spine, bone mineral density values were lower in controls than in patients (1.058 +/- 0.329 gr/cm(2) vs 1.155 +/- 0.224 gr/cm(2) respectively, P < 0.05). When premenopausal (n = 44) and postmenopausal (n = 44) patients were compared with their respective controls, bone mineral density was similar both in femoral neck and lumbar spine. The proportion of women with normal bone mass density, osteopenia and osteoporosis in patient and control groups was similar in pre- and postmenopausal women. In conclusion, long-term suppressive LT4 treatment does not appear to affect skeletal integrity in women with differentiated thyroid carcinoma.     

Bone Involvement in Primary Hemochromatosis and Alcoholic Cirrhosis

Biochemical indexes of bone metabolism, bone mineral density, and histomorphometry were evaluated in 14 male patients with noncholestatic cirrhosis due to primary hemochromatosis (six cases) or to chronic alcohol abuse (eight cases), and in 30 male controls of similar age. Alkaline phosphatase in alcoholic patients was significantly higher than in controls (mean +/- SD 50.4 +/- 33.7 vs 33.0 +/- 7.1 U/L, p less than 0.01), as was urinary hydroxyproline in both hemochromatotics and alcoholics (mean +/- SD, 44.3 +/- 8.4 and 40.4 +/- 16.8, respectively, vs 30.1 +/- 4.5 mg/g, p less than 0.001 and p less than 0.005). Bone mineral density was significantly lower in hemochromatotics than in alcoholics and controls (mean +/- SD, 591 +/- 90 vs 765 +/- 87 and 759 +/- 34 mg/cm2, respectively, p less than 0.005 and p less than 0.001). At bone biopsy, trabecular osteoporosis was observed in two hemochromatotics and four alcoholics, and osteomalacia was seen in another alcoholic. Overall densitometric and histomorphometric findings indicate a derangement of trabecular bone in both alcoholic and hemochromatotic cirrhosis, whereas cortical osteoporosis seems limited to hemochromatotic patients.     

REDUCED FOREARM BONE MINERAL CONTENT AND BIOCHEMICAL EVIDENCE OF INCREASED BONE TURNOVER IN WOMEN WITH EUTHYROID GOITRE TREATED WITH THYROID HORMONE

We used single-photon absorptiometry to assess forearm bone mineral content (BMC/BW) (arbitrary units normalized for bone width) at a proximal site (PBMC/BW) and at a more distal site (DBMC/BW) in 60 women treated with 25-50 micrograms T3 or 50-100 micrograms T4 for euthyroid goitre, in 13 untreated goitre patients, and in 2 controls matched for age and menopausal state for each goitre patient. BMC/BW was not significantly different between untreated goitre patients and controls. In 36 premenopausal patients, treated for 5.8 +/- 5.4 years (mean +/- SD) a slight decrease in PBMC/BW of about 5% compared to controls to controls was observed (PBMC/BW 1.42 +/- 0.19 vs 1.49 +/- 0.13, P less than 0.05). In 24 postmenopausal patients, treated for 10.0 +/- 5.8 year, a 20% deficit in BMC/BW compared to controls was found (DBMC/BW 0.80 +/- 0.18 vs 1.06 +/- 0.20, P less than 0.001 and PBMC/BW 1.14 +/- 0.20 vs 1.42 +/- 0.19, P less than 0.001). Biochemical indices of bone metabolism in 43 pre and post-menopausal patients and 43 controls showed in the patients a higher serum alkaline phosphatase activity (AP) (P less than 0.01 and P less than 0.05 and serum osteocalcin (NS and P less than 0.05). AP was negatively correlated with TSH levels and, in postmenopausal patients, with DBMC/BW and PBMC/BW. Our results suggest that treatment of euthyroid women with moderate doses of thyroid hormone increases bone turnover with clear adverse effects on bone mineral status in postmenopausal patients.     

Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.     

Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon

In experimental and clinical studies, conflicting results regarding the effect of oral anticoagulant therapy on bone metabolism have been reported. To measure a possible influence of long-term anticoagulant therapy with phenprocoumon on peripheral bone mass, measurements of peripheral bone mineral content (BMC) and serum osteocalcin levels were performed with single photon absorptiometry in a total of 78 patients on anticoagulant treatment. We studied 43 women (mean age 66 years +/- 2 SEM) and 35 men (mean age 65 years +/- 2 SEM) with a median duration of phenprocoumon therapy of 1 year (1-9 years). In all patients, the medical history gave no symptoms of metabolic bone disease, or diseases or medications causing osteoporosis. Both in the male and female groups, mean peripheral BMC was significantly decreased (male: P less than 0.01, female: P less than 0.003) when compared with corresponding controls. Serum OC-levels measured in 16 patients were also significantly lower than those of the controls (P less than 0.02). Our data of decreased BMC and low serum OC-levels indicate reduced bone mass in patients on long-term anticoagulant therapy with phenprocoumon. This may imply an influence of anticoagulants on bone metabolism resulting in decreased bone formation.     

The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

OBJECTIVE: Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after stopping GH treatment. SUBJECTS AND METHODS: Twenty-six (11 females) patients with idiopathic CO GHD participated. All patients but two had been treated for isolated GHD in childhood. The childhood diagnosis was established by an insulin tolerance test (ITT) and reassessed in adulthood by an ITT (N = 21) or arginine test (n = 5), revealing that 10 patients had GHD according to adult criteria. Accordingly, the patient group was divided into (1) patients who did not have persistent GHD in adulthood and (2) patients who did have persistent adult GHD. Twenty-six healthy subjects acted as age-, gender- and body mass index (BMI)-matched controls. RESULTS: The patients who did not have persistent GHD had significantly lower IGF-I values and whole-body, femoral neck and lumbar spine BMD compared to controls [0.994 +/- 0.10 vs. 1.114 +/- 0.11 g/cm2 (P = 0.003), 0.842 +/- 0.12 vs. 0.962 +/- 0.11 g/cm2 (P = 0.006) and 1.026 +/- 0.14 vs. 1.127 +/- 0.13 g/cm2 (P = 0.004), respectively]. Femoral neck BMD was significantly reduced in the patients who had persistent GHD, compared to controls (0.842 +/- 0.09 vs. 0.938 +/- 0.11, P = 0.04). Significant correlations were observed between all bone variables and IGF-I in all subjects, whereas no correlations were observed between bone variables and GH peak levels in the 26 patients. CONCLUSION: In conclusion, we found that (1) patients with idiopathic CO GHD, who at retest in adulthood did not have GHD according to adult criteria, had reduced serum IGF-I and BMD/BMC compared to controls. (2) This observation was also made in the patients who did have persistent GHD in adulthood. The findings may reflect the fact that the present diagnostic criteria for adult GHD (i.e. response to the ITT) do not reflect the clinical consequences of disordered GH-IGF axis in CO GHD young adults who were treated with GH in childhood. Alternatively, despite seemingly adequate GH treatment in childhood an optimal peak bone mass in adolescence may never have been reached in either of the groups. (3) IGF-I levels correlated with clinical signs of the adult GHD syndrome. We believe that further studies on the indications and diagnostic procedures for GH treatment after cessation of linear growth are necessary.     

Loss of bone mineral density in Chinese pre-menopausal women with systemic lupus erythematosus treated with corticosteroids

The adverse effect of disease and chronic corticosteroid therapy on bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE) has been reported in several studies of Caucasian populations. As the factors controlling bone homeostasis may be different in Asian populations, we measured BMD in 52 pre-menopausal Chinese women (mean age 34.1 +/- 8.0 yr) with SLE (mean disease duration 6.4 +/- 4.5 yr) treated with prednisone (mean daily dose 11.4 +/- 10.8 mg/day). Lumbar spine, hip (total and subregions) and total body BMDs were measured in the SLE patients using dual-energy X-ray absorptiometry (DEXA), and compared with those from healthy controls matched for age, sex and body mass index. Compared to controls, SLE patients were found to have lower BMD (g/cm2) at several sites: the lumbar spine (0.98 vs 0.90, P = 0.001), Ward's triangle (0.72 vs 0.67, P = 0.03), total body (1.04 vs 1.01, P = 0.04) and total hip (0.87 vs 0.82, P = 0.05). There was no correlation between BMD at any region and duration of disease, activity of disease or prednisone therapy (mean daily dose, cumulative dose or treatment duration). When BMDs were compared between controls and SLE patients, subgrouped according to those not on calcium and those arbitrarily receiving calcium supplements (1 g/day), significantly lower BMDs were found in those not on calcium compared to both controls and SLE patients on calcium. BMDs in SLE patients on calcium were not different from those in controls. The low prevalence of osteoporosis in our SLE patients (4-6%) suggests significant loss of BMD in Chinese SLE patients on corticosteroid therapy is less than that reported in Caucasians (12-18%).      

Bone mineral density and bone markers in hypogonadotropic and hypergonadotropic hypogonadal men after prolonged testosterone treatment

After prolonged treatment (76.4+/-10 and 70.1+/-12.3 months, respectively) (mean+/-SE) with testosterone enanthate (250 mg i.m. every 3 weeks), bone mineral density (BMD) and bone metabolism were evaluated in 12 patients (aged 29.3+/-1.4 yr) affected by idiopathic hypogonadotropic hypogonadism (IHH), in 8 patients (29.6+/-2.6 yr) affected by Klinefelter's syndrome (KS), and in 10 healthy men (30.6+/-1.7 yr) matched according to age and BMI. Spinal BMD in IHH was significantly lower than in controls (0.804+/-0.04 vs 1.080+/-0.01 g/cm2; p<0.001), while there was no difference in neck BMD (0.850+/-0.01 vs 0.948+/-0.02 g/cm2). Neither spinal (0.978+/-0.05 g/cm2) nor neck (0.892+/-0.03 g/cm2) BMD in KS were significantly different from controls. Six IHH and one KS subjects were osteoporotic, while 6 IHH and 2 KS subjects were osteopenic. A significant inverse correlation was found between spinal BMD and age at the treatment onset in IHH (r=-0.726, p=0.007). In IHH there were significant increases in bone formation (alkaline phosphatase=318.3+/-33.9 vs 205.4+/-20.0 IU/l; osteocalcin=13.44+/-1.44 vs 8.57+/-0.94 ng/ml; p<0.05) and in bone resorption (urinary cross-linked N-telopeptides of type I collagen=149.1+/-32.3 vs 47.07+/-8.4 nmol bone collagen equivalents/mmol creatinine; p<0.05) compared to controls, while such differences were not present in KS. Our results outline the importance of BMD evaluation in all hypogonadal males. Nevertheless, bone loss is a minor characteristic of KS, while it is a distinctive feature of IHH. Therefore, early diagnosis and age-related replacement therapy coupled with a specific treatment for osteoporosis could be useful in preventing future severe bone loss and associated skeletal morbidity.     

Parathyroid hormone deficiency and excess: similar effects on trabecular bone but differing effects on cortical bone

Parathyroid hormone (PTH) may be anabolic at trabecular bone and catabolic in cortical bone. As many regions of the skeleton contain both types of bone, the effects of PTH deficiency or excess may be difficult to evaluate using bone densitometry, a technique that integrates the cortical and trabecular compartments of bone. We asked the following questions: 1) Is the higher bone mineral density (BMD) in postsurgical hypoparathyroidism due to higher cortical, not trabecular, bone? 2) Is age-related bone loss slowed in patients with postsurgical hypoparathyroidism? 3) Is lower BMD in primary hyperparathyroidism the result of deficits in cortical, not trabecular, bone? BMD of the lumbar spine, proximal femur, distal radius, and femoral midshaft was measured by postero-anterior (PA) scanning, while bone mineral content (BMC) of the third lumbar vertebra was measured by lateral scanning using dual x-ray absorptiometry in 10 women, ages 64.6 +/- 3.2 yr, with postsurgical hypoparathyroidism and in 25 women, ages 68.7 +/- 1.6 yr, with primary hyperparathyroidism. Measurements were repeated 4.7 +/- 0.6 yr later in 8 patients with hypoparathyroidism and 4.0 +/- 0.4 yr later in 20 age-matched controls. Data were expressed as z scores (SD, mean +/- sem) derived from 405 postmenopausal women. In patients with hypoparathyroidism, bone mass z score of the third lumbar vertebra (vertebral body plus posterior processes) was higher than zero by PA scanning (1.26 +/- 0.58 SD, P < 0.05) and lateral scanning (1.04 +/- 0.60 SD, P = 0.1), and higher at the trabecular-rich vertebral body (1.02 +/- 0.47 SD, P = 0.07) and predominantly cortical posterior processes (0.98 +/- 0.66 SD, P = 0.1) determined by lateral scanning. The BMD z scores were higher than zero at the femoral neck (0.89 +/- 0.48 SD, P = 0.09), but not at the femoral midshaft (0.45 +/- 0.60, NS) and distal radius (0.04 +/- 0.51, NS). During follow-up, femoral neck BMD decreased in controls but not in patients with hypoparathyroidism (slope, -0.00818 +/- 0.00496 g/cm2/year vs. 0.00907 +/- 0.00583 g/cm2/year, respectively, P = 0.06). There was no change in lumbar spine BMD in either group. In 25 women with primary hyperparathyroidism, there were no deficits in BMD at the third lumbar vertebra (vertebral body plus posterior processes) by PA or lateral scanning. By lateral scanning, BMC was increased at the vertebral body (0.64 +/- 0.31 SD, P < 0.01) and reduced at the posterior processes (-0.65 +/- 0.26 SD, P < 0.05). BMD was lower at the midshaft of the femur (-0.82 +/- 0.37 SD, P < 0.05) and at the distal radius (-0.68 +/- 0.20 SD, P < 0.01), but not at the femoral neck (-0.08 +/- 0.20 SD, NS). Longitudinal data were unavailable in hyperparathyroid patients. In summary, trabecular bone is increased by both PTH deficiency and excess. Cortical bone loss is slowed by PTH deficiency and accelerated by PTH excess so that suppression of PTH may reduce age-related bone loss and the risk of fracture. Assessment of BMD in PTH deficiency and excess requires the separate study of cortical and trabecular bone.     

Normal bone density of the wrist and spine and increased wrist fractures in girls with Turner's syndrome.

Turner's syndrome is associated with multiple skeletal abnormalities, including osteoporosis. We evaluated the hypothesis that girls with Turner's syndrome may have deficient bone density before the expected age of pubertal onset (9-13 yr) by comparing the bone mineral content of the wrist and lumbar spine in 78 girls with Turner's syndrome (4-13 yr old) and 28 normal prepubertal girls who were matched for age, bone age, body mass index, or height age. The bone mineral content of the wrist and spine was measured by single photon absorptiometry (SPA) and dual photon absorptiometry (DPA), respectively. SPA values for girls with Turner's syndrome vs. normal subjects (4-6.9, 7-9.9, and 10-12.9 yr old) were (mean +/- SD) 0.27 +/- 0.05 vs. 0.36 +/- 0.05, 0.35 +/- 0.06 vs. 0.41 +/- 0.06, and 0.41 +/- 0.05 vs. 0.45 +/- 0.03 g/cm2, respectively. SPA values in the Turner's syndrome girls were decreased compared to those in normal prepubertal girls, matched for age (P less than 0.0001), bone age, (P less than 0.001), and body mass index (BMI; P less than 0.0001), but not for height age. DPA values for girls with Turner's syndrome vs. normal girls in the same age categories were 0.65 +/- 0.06 vs. 0.70 +/- 0.09, 0.77 +/- 0.08 vs. 0.79 +/- 0.09, and 0.83 +/- 0.12 vs. 0.78 +/- 0.07 g/cm2. DPA values in Turner's syndrome girls (as a group) were decreased compared to those in normal prepubertal girls matched for age (P less than 0.05) and BMI (P less than 0.02), but not for bone age or height age. The annual incidence rate of wrist fractures in Turner's syndrome girls (9.1 of 1000) was significantly increased compared to the reported annual incidence rate in normal children (3.5 of 1000; P less than 0.003). We conclude that prepubertal-aged girls with Turner's syndrome (less than 13 yr old) have normal bone density for height age, but significantly decreased bone density of the wrist for chronological age, bone age, and BMI. They also have significantly more wrist fractures than normal girls, but it is not clear that this is related to their bone density.     

Thyroid function and bone turnover

The mechanism of thyroid action on bone was studied in 15 patients with thyrotoxicosis and 14 patients with hypothyroidism. The patients were studied twice: when they were thyrotoxic or hypothyroid and when they had returned to a euthyroid state. Parameters of bone turnover showed a decrease when hyperthyroid patients became euthyroid: serum calcium (2.51 +/- 0.04 vs 2.38 +/- 0.03 mmol/l, P less than 0.05), acid phosphatase (11.7 +/- 0.7 vs 8.3 +/- 0.4 U/l, P less than 0.01), alkaline phosphatase (124 +/- 11 vs 98 +/- 8 U/l, P less than 0.05), the calcium/creatinine ratio (1.03 +/- 0.31 vs 0.43 +/- 0.07, P less than 0.01) and the hydroxyproline/creatinine ratio in the urine (69.9 +/- 12 vs 20.7 +/- 2.4, P less than 0.01). These parameters showed an increase when hypothyroid patients became euthyroid: serum calcium (2.36 +/- 0.03 vs 2.48 +/- 0.04 mmol/l, P less than 0.01), alkaline phosphatase (60 +/- 4 vs 84 +/- 8 U/l, P less than 0.05) and the hydroxyproline/creatinine ratio in the urine (15.9 +/- 4.3 vs 25.3 +/- 3.2, P less than 0.05). Changes in the calcium regulating hormones, parathyroid hormone, calcitonin and vitamin D metabolites, were not observed when hyperthyroid patients became euthyroid. When hypothyroid patients were treated a decrease in serum levels of 1.25-dihydroxyvitamin D (32.6 +/- 4.6 vs 17.9 +/- 2.5 ng/l, P less than 0.01) was observed. Serum growth hormone levels decreased when hypothyroid patients became euthyroid (4.3 +/- 0.5 vs 2.6 +/- 0.4 mU/l, P less than 0.01). The possible mechanisms of thyroid action on bone are discussed. The presented findings are in accordance with a direct effect of thyroid hormones on bone in thyrotoxicosis. An additional factor could be somatomedin, that might also be involved in changes in bone turnover in hyper- and hypothyroidism.     

Low serum estradiol levels in subjects with arterial calcification

The relationship between arterial calcification and serum estradiol levels was studied in 72 postmenopausal female and 59 male subjects. In both sexes, subjects with iliac artery calcification had rather lower serum estradiol levels (8.4 +/- 1.4 pg/ml in the females, and 19.2 +/- 2.5 pg/ml in the males) than controls (16.1 +/- 1.6 pg/ml in the females, and 29.7 +/- 2.4 pg/ml in the males). The bone mineral content of females with iliac artery calcification (0.44 +/- 0.02 g/cm2) was lower than controls (0.52 +/- 0.01 g/cm2); a positive correlation between serum estradiol levels and bone mineral content was found in the females. However, bone mineral content did not significantly differ between males with and without arterial calcification (0.67 +/- 0.03 g/cm2 in the former, and 0.65 +/- 0.02 g/cm2 in the latter). These results indicate that arterial calcification and increased bone resorption are both individual results of estrogen deficiency.     

Abnormal bone mineral accrual in adolescent girls with anorexia nervosa

Anorexia nervosa (AN) is increasingly common in adolescent girls and occurs at a time of peak bone mass formation. Osteopenia is common in adolescent girls with AN, and in a cross-sectional study, we have reported low bone formation markers in such girls. To determine the impact of chronic undernutrition on bone mineral accrual in contrast to healthy controls, we prospectively measured bone mineral density (BMD) and body composition by dual energy x-ray absorptiometry, bone metabolism markers, and nutritional and hormonal status at baseline, 6 months, and 12 months in 19 adolescent girls with AN (mean +/- SEM, 15.4 +/- 0.4 yr) and 19 controls of comparable chronological and skeletal age. Overall, nutritional status in subjects with AN improved (mean percentage increase in body mass index from baseline, 9.2 +/- 1.9% and 15.2 +/- 2.6% at 6 and 12 months, respectively), with 11 subjects having recovered weight at 12 months. However, lumbar BMD at 12 months (AN, 0.88 +/- 0.02 g/cm(2), vs. control, 0.98 +/- 0.03 g/cm(2); P = 0.008) remained significantly reduced in AN compared with controls, even in recovered subjects. This was due to significant increases in lumbar BMD in controls vs. no change in AN subjects over the year (0.003 +/- 0.001 g/cm(2).month vs. 0.000 +/- 0.001 g/cm(2).month, respectively; P = 0.04). The most significant determinant of change in lumbar BMD at 12 months was change in lean body mass in both AN (r = 0.62; P = 0.008) and control (r = 0.80; P = 0.0006) groups. There were significant increases in surrogate markers of bone turnover in subjects with AN compared with controls as assessed by osteocalcin (AN, 0.9 +/- 0.4 micro g/liter.month, vs. control, -1.1 +/- 0.4 micro g/liter.month; P = 0.0007), bone-specific alkaline phosphatase (AN, 0.6 +/- 0.5 U/liter.month, vs. control, -1.5 +/- 0.4 U/liter.month; P = 0.002), deoxypyridinoline [AN, 0.1 +/- 0.1 nmol/mmol creatinine (cr).month, vs. control, -0.4 +/- 0.1 nmol/mmol cr.month; P = 0.005], and N-telopeptide (AN, 4 +/- 4 nmol BCE/mmol cr/month, vs. control, -9 +/- 4 nmol BCE/mmol cr/month; P = 0.01). Changes in IGF-I levels over the year were highly correlated with changes in bone turnover over the same period in AN (osteocalcin, r = 0.77; P = 0.001; deoxypyridinoline, r = 0.66; P = 0.01). A rise in N-telopeptide over the year was correlated with an increase in all bone mineral measures, including lumbar bone mineral content (r = 0.58; P = 0.03) and BMD (r = 0.53; P = 0.05) and total bone mineral content (r = 0.69; P = 0.006) and BMD (r = 0.69; P = 0.006) in the AN group. Therefore, despite recovery over 1 yr, poor bone mineral accrual persists in adolescent girls with AN in contrast to rapid bone accrual in healthy girls. Normalization of bone turnover markers occurs in association with nutritional recovery and an increase in the nutritionally dependent bone trophic factor IGF-I. A rise in bone turnover markers may be an early indicator of increase in BMD in recovering girls with AN.     

Low bone density is an etiologic factor for stress fractures in athletes

OBJECTIVE: To determine whether low bone density and other risk factors for osteoporosis are associated with stress fractures in athletes. DESIGN: Case-control study. SETTING: Institutional sports injury clinic with primary and secondary care. PARTICIPANTS: Twenty-five athletes (nineteen women) with scintigraphically confirmed stress fractures matched for sex, age, weight, height, and exercise history with 25 control athletes with no history of bone injury. MEASUREMENTS AND MAIN RESULTS: Bone mineral density measured by dual-energy x-ray absorptiometry was significantly lower in athletes with fractures than in control athletes: In the spine, bone mineral density was 1.01 +/- 0.14 g/cm2 in athletes with fractures and 1.11 +/- 0.13 g/cm2 in control athletes (P = 0.02). In the femoral neck, it was 0.84 +/- 0.09 g/cm2 in athletes with fractures and 0.90 +/- 0.11 g/cm2 in control athletes (P = 0.005). It was also significantly lower in the Ward triangle (P = 0.01) and the greater trochanter (P = 0.01). Eight athletes with fractures and no control athletes had less than 90% of predicted age-related spine density (P = 0.01), and three athletes with fractures had bone mineral densities that were 2 SDs or more below this predicted level. More athletes with fractures than control athletes had current menstrual irregularity (amenorrhea or oligomenorrhea) (P less than 0.005). Fewer athletes with fractures were using oral contraceptives (P less than 0.05). Seven-day diet records indicated similar energy and nutrient intakes, except athletes with fractures had lower calcium intakes (697 +/- 242 mg/d compared with 832 +/- 309 mg/d; P = 0.02). Dairy product intake was lower in athletes with fractures since leaving high school (P less than 0.05). The incidence of a family history of osteoporosis was similar in both groups. CONCLUSIONS: In athletes with similar training habits, those with stress fractures are more likely to have lower bone density, lower dietary calcium intake, current menstrual irregularity, and lower oral contraceptive use.     

Bone status and fracture prevalence in Russian adults with childhood-onset growth hormone deficiency

The consequences of lifelong untreated childhood-onset GH deficiency (COGHD) on adult bone and especially fracture prevalence are largely unknown due to the lack of data on long-term outcome of untreated patients. Therefore, we studied adult Russian patients (n = 66; 28 females and 38 males) with idiopathic GH-untreated COGHD. Patients had isolated GH deficiency (IGHD; n = 18, age 23 +/- 10 yr) or multiple pituitary hormone deficiency (MPHD) with open (OMPHD; n = 27, age 23 +/- 5 yr) or closed growth plates (CMPHD; n = 21, age 55 +/- 12 yr). Bone mineral content (BMC) and bone mineral density (BMD) values were compared with 821 normal Russian controls. Fracture prevalence was ascertained from medical history and compared with similar data from 333 normal controls.Height sd score was -4.6 (range, -1.8 to -8.1). This represents 82% of the height of normal Russian adults. BMC of the lumbar spine, femoral neck, and total body of patients with IGHD was 54, 71, and 59%, respectively, of that of age- and sex-matched controls (all P < 0 0.001). A similarly decreased BMC (42-69% of expected values) was found for all bone regions of patients with both OMPHD and CMPHD. Mean areal BMD measurements (g/cm(2)) varied (Z scores between -1.8 and -3.0), but the calculated true bone density (g/cm(3)) was normal in patients with IGHD or CMPHD and only slightly decreased (Z score, -0.8) in patients with OMPHD. Lifetime low-energy fracture prevalence was normal in patients with IGHD but substantially exceeded the expected prevalence in OMPHD (odds ratio of fracture = 3.0; 0.6 fractures per patient; P < 0.0001) or CMPHD patients (odds ratio for fracture = 7.4; 2.2 fractures per patient; P < 0.0001).In conclusion, IGHD and MPHD of childhood onset very substantially impair adult height and BMC. Although areal BMD is frankly decreased, volumetric bone density is unaffected, but nevertheless, the fracture prevalence in patients with MPHD is markedly increased. These observations demonstrate that not only volumetric density but also bone mass and shape are major determinants of bone strength.     

Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome

Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.