Abnormalities in bone mineral density and bone histology in thalassemia.

This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF-I was reduced and may modulate the reduction of bone mass. INTRODUCTION: Bone histomorphometric studies in thalassemia to show alterations in bone histology and their relationship to biochemical parameters are very limited. Therefore, this study was systematically conducted to determine the alterations in thalassemia patients. METHODS: Serum biochemical parameters, trans-iliac crest bone biopsy, and determination of bone mineral density of femur and lumbar spine were done in 18 thalassemic patients (10 females and 8 males). RESULTS: Serum osteocalcin, carboxy terminal teleopeptide fragment of type I collagen, and parathyroid hormone levels were within normal limits, but serum 25(OH) vitamin D (19.3 +/- 1.6 ng/ml) and 1,25(OH)2 vitamin D (33.77 +/- 1.51 pg/ml) levels were decreased. Serum insulin-like growth factor I (IGF-I; 145.2 +/- 20 ng/ml) was suppressed, whereas serum ferritin (1366.6 +/- 253.9 ng/ml) was markedly elevated. Reduced bone mineral density was found in all studied areas. Trabecular bone volume was significantly decreased (16.65 +/- 1.12%), whereas bone formation rate, eroded surface, and other bone histomorphometric parameters were within normal limits. The trabecular bone volume varied significantly with bone mineral density of total femur (r = 0.48, p = 0.04). There was an extensive stainable iron surface on the mineral front (9-60%). Significant correlation between serum IGF-I, serum ferritin, stainable iron surface, and bone mineral density, lumbar spine, and total femur were found. Serum IGF-I correlated with trabecular bone volume (r = 0.6, p = 0.03), inversely with both serum ferritin level (r = -0.6, p < 0.01), and inversely with stainable iron surface (r = -0.53, p = 0.02). Multiple regression analysis demonstrated that IGF-I was the only independent variable that determined bone mineral density of lumbar spine and total femur. CONCLUSION: Low bone mineral density and reduced trabecular bone volume with extensive iron deposition are the predominant findings in thalassemic patients. There was no evidence of increased bone resorption or mineralization defect. A reduction in circulatory IGF-I may modulate the reduction of bone mass.     

Vitamin D status and bone health in healthy Thai elderly women

Objective

The prevalence of hypovitaminosis D varies in different countries. Therefore, the current study was designed to assess vitamin D status and bone health in elderly women in Thailand, which is situated near the equator.

Methods

This cross-sectional study was performed in 446 healthy women aged 60-97 y.

Results

Serum 25-hydroxyvitamin D (25(OH)D) was 67.6 ± 15.7 (mean ± SD) nmol/L. Daily calcium intake was 309.5 ± 147.2 mg/d. Serum 25(OH)D levels tended to decline with bone mineral density (BMD) status. Based on functional health-based reference values, plasma-intact parathyroid hormone began to rise below serum 25(OH)D level 70 nmol/L and increase significantly when serum 25(OH)D was ≤60 nmol/L. Thirty-two percent of elderly women had 25(OH)D insufficiency (≤60nmol/L). There was no trend toward a decrease in the concentration of serum 25(OH)D with age (r = −0.078, P = 0.10) and no significant inverse relationship with plasma intact parathyroid hormone values (r = −0.079, P = 0.097). However, a positive relationship was observed between serum 25(OH)D level and femoral neck BMD (r = 0.156, P = 0.001) but not lumbar spine L₂-L₄ BMD (r = 0.093, P = 0.050). In addition, BMD at the femoral neck but not lumbar spine of the vitamin D insufficiency group was significantly lower than that of the vitamin D sufficiency group.

Conclusion

The optimum level of serum 25(OH) value in Thai elderly women should be higher than 70 nmol/L. Vitamin D insufficiency is observed in one-third of elderly women in Bangkok.     

Genetic variant in the aquaporin 9 gene is associated with bone mineral density in postmenopausal women

This study investigated whether single nucleotide polymorphisms (SNP) in the aquaporin 9 (AQP9) gene is associated with bone mineral density (BMD) in Thai postmenopausal women, after an initial genome-wide screening using high-throughput SNP genotyping in pooled DNA samples. Subjects consisted of 516 postmenopausal women aged 50 or more. High-throughput SNP screening was performed by comparing the estimated allele frequency derived from hybridization signal intensities of pooled DNA samples on the Affymetrix 500 K SNP genotyping chip set. The SNP was then genotyped for each subject individually. Data were expressed as mean ± SEM. Pooled DNA SNP screening revealed the allele frequency of an intronic A/T SNP rs2414539 in the AQP9 gene as being different between subjects with femoral neck BMD in tertiles 1 and 3. Individual genotyping in all subjects revealed that femoral neck BMD in subjects with TT, TA, and AA genotypes were 0.79 ± 0.06 (n = 3), 0.75 ± 0.01 (n = 98), and 0.71 ± 0.01 g/cm(2) (n = 415), respectively. The presence of the T allele in rs2414539 was associated with femoral neck BMD (r = 0.11, P < 0.05) but not with lumbar spine BMD. The relationship was still significant after controlling for body weight and age (P < 0.05). Genetic variation in the AQP9 gene is associated with femoral neck BMD in postmenopausal women, and may represent one of the susceptibility genes for phenotypes related to bone mass.     

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.     

Biochemical markers of bone turnover and response of bone mineral density to intervention in early postmenopausal women: an experience in a clinical laboratory

BACKGROUND: Markers of bone formation and resorption may be useful as early indicators of response to therapy. Our aim in this study was to investigate the use of bone markers for monitoring of intervention for bone loss in early postmenopausal women and to assess the relationships between these markers and changes in bone mineral density (BMD). METHODS: Subjects were randomly assigned to the following groups: a control group; a group receiving calcium alone; groups receiving calcium plus low or conventional doses of conjugated equine estrogen; and groups receiving calcium plus low or conventional doses of calcitriol. At baseline and at 1 and 3 months after intervention, we measured serum intact osteocalcin, serum N-terminal midfragment osteocalcin, serum C-terminal telopeptide of type I collagen (CTx), urinary deoxypyridinoline cross-links, and urinary CTX: The BMD of the lumbar spine and the femoral neck was measured at baseline and after 1 and 2 years of intervention. RESULTS: No marker changed significantly in the control group except urinary CTx, which increased at 3 months. Serum CTx decreased in all regimens at 1 or 3 months of intervention. In addition, the changes of all markers at 3 months were inversely associated with the change in the BMD of the lumbar spine at 1 or 2 years (r = -0.144 to -0.314), whereas only the changes of bone resorption markers at 3 months were inversely correlated with the changes in femoral BMD at 1 or 2 years (r = -0.143 to -0.366). CONCLUSIONS: Biochemical markers of bone turnover appear to be of use in assessing early response to therapy. Bone resorption markers, especially serum CTx, are better indicators than bone formation markers for estimating the response to intervention in early postmenopausal women. However, the early changes in bone markers were weakly related to the later changes in BMD.     

Preevacuation Serum CA 125 in Complete Hydatidiform Mole

Studies on CA 125 in hydatidiform mole are limited. The objective of this study was to measure the preevacuation serum CA 125 level in patients with complete hydatidiform mole and to determine whether it could predict the later development of persistent trophoblastic disease. Preevacuation serum CA 125 levels were immunoradiometrically measured in 69 patients with histologically confirmed complete hydatidiform mole. The mean (range) serum CA 125 level was 63.7 (10.5–404.7) U/ml. Using 35 U/ml as the cutoff point, the elevated CA 125 levels were observed in 53.6% (37/69) of the patients. The mean serum CA 125 level of patients who later developed persistent trophoblastic disease was not significantly higher than that of those who had benign course (78.9 vs 52.6 U/ml,P> 0.05). In conclusion, the preevacuation serum CA 125 level was elevated in about half of patients with complete hydatidiform mole and it could not be used to predict the subsequent development of persistent trophoblastic disease.     

Effect of alendronate on bone mineral density and bone turnover in Thai postmenopausal osteoporosis

Alendronate has recently been approved for the prevention and treatment of postmenopausal osteoporosis, and its efficacy has been demonstrated in many Western countries. Our present study was performed to evaluate the effect of alendronate on bone mineral density (BMD) and its tolerability in Thais. Eighty postmenopausal women with osteoporosis participated in this study. After giving informed consent, the subjects were randomly allocated either 10mg alendronate or placebo in a double-blind fashion. All patients received a supplement of 500mg elemental calcium daily. BMD at the lumbar spine, femoral neck, and distal forearm was measured at baseline and 6 and 12 months after treatment. Biochemical markers of bone resorption were determined at baseline and 6 months after treatment. Baseline characteristics were similar in both alendronate- and placebo-treated groups. Ten subjects discontinued the study. Of 70 subjects, 32 received 10mg alendronate daily and the remaining subjects received placebo. At 1 year, BMD in the alendronate-treated group had increased from baseline by 9.2%, 4.6%, and 3.1% at lumbar spine, femoral neck, and distal forearm, respectively. These percentages were greater than those in controls (4.1%, 0.6%, and 1.0%, respectively). Urinary N-terminal telopeptide (NTx)-I and serum C-terminal telopeptide (CTx)-I levels decreased in both groups after 6 months of treatment. However, more reduction was demonstrated in the alendronate-treated group (71.9% vs. 28.4%, P 0.01, and 84.7% vs. 33.1%, P 0.01, respectively). Compliance with treatment and drug tolerability were good in both alendronate and placebo groups. We concluded that treatment with alendronate 10mg daily for Thai postmenopausal women with osteoporosis significantly increased BMD at all skeletal sites and reduced biochemical markers of bone resorption. It was well tolerated without any serious side effects.     

Contribution of lean tissue mass to the urban-rural difference in bone mineral density

While the urban-rural difference in bone mineral density (BMD) has been shown in some, but not all, Western populations, such a difference and the reason for the difference is largely unknown, particularly in developing countries. This cross-sectional, epidemiologic study was designed to examine the hypothesis that differences in measures of body composition such as lean mass (LM) and fat mass (FM) contribute to the urban-rural difference in BMD. Lean mass, fat mass, lumbar spine and femoral neck BMD were measured by DXA (GE Lunar Corp, Wis.) in 411 urban (Bangkok city) and 436 rural (Khon Kaen province) Thai subjects, aged 20–84 years. Rural men and women had significantly higher LM and lower FM than their urban counterparts. In multiple linear regression analysis, age, LM, menopausal status (in women) and residence were independent determinants of BMD. After adjusting for age, menopause and LM, rural subjects were found to have significantly higher femoral neck BMD, but not lumbar spine BMD, than urban subjects. Furthermore, to alleviate the potential effect of multicolinearity of LM and FM, each rural subject was matched with each urban subject for FM and age, which resulted in 46 pairs of men and 91 pairs of women. In this matched-pair analysis, the femoral necks in rural men and women were, respectively, 7.3±2.1% (mean±SE; P <0.01) and 6.3±2.8% ( P <0.02) higher than in urban men and women. The urban-rural difference in LM accounted for approximately 23 and 5% of the urban-rural difference in femoral neck BMD in men and women, respectively. These data are thus consistent with the hypothesis that the urban-rural difference in BMD at a weight-bearing site is in part associated with the urban-rural difference in lean mass.     

Vitamin D status in Thai dermatologists and working‐age Thai population

This study aimed to determine the prevalence of vitamin D insufficiency among Thai dermatologists compared with the general working‐age population in Bangkok. A cross‐sectional study was conducted in healthy Thai physicians who had at least 1 years’ experience in dermatology practise and a subsample of the general Thai population from the Fourth National Health Survey. Serum 25‐hydroxyvitamin D (25[OH]D), a combination of 25(OH)D2 and 25(OH)D3, levels in both groups were measured using liquid chromatography coupled with mass spectrometry. The majority of dermatologists were of Fitzpatrick skin type III (n = 61, 61.3%) or IV (n = 32, 33.3%). The mean serum 25(OH)D and 25(OH)D3 levels were 18.9 and 18.2 ng/mL, respectively, whereas the corresponding levels in the general population were 26.5 and 25.8 ng/mL. None of the dermatologist had serum 25(OH)D sufficiency (>30 ng/mL), 38 (38.78%) had vitamin D insufficiency (20–30 ng/mL) and 60 (61.22%) had vitamin D deficiency (<20 ng/mL). The frequency of vitamin D deficiency in dermatologists was significantly higher than in the general population (61.2% vs 19.2%, P < 0.001). Ninety percent of dermatologists used sunscreen daily and spent time mostly indoors. Dermatologists used physical sun‐protection more than half of the time when outdoors, for example, a book or paper as a sunshade (70.3%), an umbrella (48.4%), a long‐sleeved shirt (20.4%) or a hat (9.7%). In conclusion, dermatologists showed a remarkably high prevalence of vitamin D deficiency which may be due to inadequate exposure to sunlight, regular use of sunscreen and practicing various sun‐protection activities.