Manuel Sosa

Bone mineral metabolism is normal in non-insulin-dependent diabetes mellitus

Because of the previous controversial findings in non-insulin-dependent diabetes mellitus (NIDDM), we measured bone-mineral density (BMD) by two different methods, studied biochemical markers of bone remodeling and calciotropic hormones (parathyroid hormone and calcitonin) in women with NIDDM, and compared the results with age-matched controls. Forty-seven women with NIDDM and 252 healthy nondiabetic women as controls were recruited for this study. BMD was measured by dual X-ray absorptiometry (DEXA) and by quantitative computed tomography (QCT). Biochemical markers of bone remodeling included plasma alkaline phosphatase (AP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), calcitonin (CT), and 24-h urine calcium, hydroxyproline. Diabetic patients were more obese with a higher body-mass index (BMI) than controls. Bone mass was normal in NIDDM, both by DEXA and by QCT. Biochemical markers of bone remodeling, PTH and CT were also normal. There was no statistical correlation between bone mass and any of the other measurements studied. There is no evidence that NIDDM produces any change in bone metabolism or mass.

Quantitative Ultrasound Calcaneus Measurements: Normative Data and Precision in the Spanish Population

Abstract:Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. In this study we have determined the normative QUS data in the Spanish population for the Sahara Clinical Sonometer (Hologic). Broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were determined. We also studied the precision in vivo and in vitro. The short-term in vivo precision (CV) was 4.88% for BUA, 0.36% for SOS, 3.45% for QUI and 4.15% for BMD, while in vitro precision was 0.40% for SOS and 2.67% for BUA. Our results are comparable to reference population data previously published in other countries and may serve as reference normative data for both genders in Spain.

The range of bone mineral density in healthy Canarian women by dual X-ray absorptiometry radiography and quantitative computer tomography.

Bone mass measurements play a crucial role in the diagnosis of osteoporosis. According to a World Health Organization (WHO) Working Group, osteoporosis in women can be diagnosed if the value for bone mineral density (BMD) is 2.5 or more standard deviations below the mean value of a young reference population. This definition obviously requires the availability of normal data, which should ideally be obtained locally. The objective was establish normal values of BMD in the female Canarian population, by dual X-ray absorptiometry (DXA) in the lumbar spine and the proximal femur, and by quantitative computed tomography (QCT) in the lumbar spine, and to study the correlation between the results of both techniques and the changes with age. Seven hundred forty-four Healthy Canarian women, from 20-80 yr old were examined. Measurement of bone density was performed by an Hologic QDR 1000 densitometer (DXA) in the lumbar spine and proximal femur, and by a Toshiba scanner model 600 HQ in the lumbar spine. Both methods show that the peak bone mass is achieved in the fourth decade (30-39 yr). Bone density decreases thereafter with age in the lumbar spine (r = -0.3364 DXA and r = -0.6988 for QCT) and in the femoral neck (r = -0.3988). Bone density mean values obtained by DXA are very similar to those described in Spain and in other European female populations, using the same densitometer. The correlations between both techniques (DXA and QCT) were high and statistically significant (p < 0.001 in every case). Normal values in the normal Canarian women for DXA and QCT are provided. Our results are very similar to those previously described. These two techniques have a close correlation.

Bone mineral density and risk of fractures in aging, obese post-menopausal women with type 2 diabetes. The GIUMO Study.

Background and aims: Type 2 diabetes mellitus (DM) has a high prevalence in aging obese postmenopausal women. It is not clear whether or not diabetes produces an increase in bone mineral density or an increase in fracture rates. Objective: The main objective of this study was to investigate whether type 2 DM produces a higher prevalence of vertebral, hip and non-vertebral fractures in obese postmenopausal Caucasian women. A secondary objective was to study the influence of DM in quantitative ultrasound measurements of the heel (QUS) and bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), in both lumbar spine (L2–L4) and proximal femur. Method: This study was a prospective cohort of 111 patients with type 2 DM and 91 control individuals (CTR) over age 65 and obese, recruited from 16 centers in Spain. Main Outcome Measures: Lateral dorsal and lumbar X-rays were performed to assess vertebral fractures. Hip and non-vertebral fractures were noted from medical records, written reports or X-ray studies. QUS measurements were made of the calcaneus and BMD measurements of the lumbar spine (L2–L4) and proximal femur. Results: Patients had higher BMD in the lumbar spine (L2–L4) than controls (0.979 g/cm2 vs 0.927 g/cm2, p=0.035), but we found no statistically significant differences in the proximal femur. QUS measurements showed similar values in both groups: BUA (69.3 dB/Mhz vs 66.7 dB/Mhz, p=0.291), SOS (1537 m/sg vs 1532 m/sg, p=0.249) and QUI (87.5 vs 83.7, p=0.153). No statistically significant differences were found in any case. There was no association between vertebral, hip and non-vertebral fractures and DM. The crude odds ratio, without adjusting was 1.045 (CI 957o 0.531; 2.059), and the adjusted odds ratio was 0.927 (CI 95% 0.461; 1.863). Conclusions: In obese postmenopausal Caucasian women, type 2 DM produces an increase in BMD of the lumbar spine without changes in BMD of the proximal femur or in QUS measurements of the heel. The prevalence of vertebral, hip and non-vertebral fractures did not increase in type 2 DM.

Osteoporosis and metabolic syndrome according to socio‐economic status, contribution of PTH, vitamin D and body weight: The Canarian Osteoporosis Poverty Study (COPS)

Poverty is associated with a great number of diseases, but the prevalence of vitamin D deficiency, secondary hyperparathyroidism and the potential association of osteoporosis, osteoporotic fractures and metabolic syndrome in this situation are less well known.

Bone Mass, Bone Turnover, Vitamin D, and Estrogen Receptor Gene Polymorphisms in Male to Female Transsexuals: Effects of Estrogenic Treatment on Bone Metabolism of the Male

The effect of chronic administration of estrogens on bone and mineral metabolism in men is not known. We have studied the effect of chronic administration of estrogens on bone mineral metabolism in a group of transsexual (TS) Canarian men, who were taking estrogens for a minimum of 3 years. This is a cross-sectional study of cases and controls and we studied biochemical markers of bone remodeling, bone mineral density (BMD), and selected biochemical and hormonal features. TS subjects had shorter stature than controls, and after adjusting for height and weight, we found that they had lower values for serum-free testosterone and higher values for BMD, both in the lumbar spine and in femoral neck. Biochemistry, bone remodeling markers, and calcitropic hormone values were similar in both groups. Finally, the distributions of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba) polymorphisms were also similar in both groups. We conclude that the chronic administration of estrogens in men may produce an increase in serum estradiol, a decrease in free testosterone levels, and an increase in BMD-both in lumbar spine and in femoral neck. We found no association between the transsexual phenotype and the distribution of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba).

The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism

Abstract. Sosa M, Torres A, Martín N, Salido E, Limiñana JM, Barrios Y, de Miguel E, Betancor P (University Hospital Insular, Bone Metabolic Unit, University of Las Palmas de Gran Canaria, Las Palmas and University of La Laguna, Canary Islands, Spain). The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism. J Intern Med 2000; 247: 124–130.

Postmenopausal Canarian women receiving oral glucocorticoids have an increased prevalence of vertebral fractures and low values of bone mineral density measured by quantitative computer tomography and dual X-ray absorptiometry, without significant changes in parathyroid hormone

BACKGROUND Daily doses higher than 7.5 mg/daily of prednisone or equivalents confer a great risk of vertebral and hip fractures with a clear dose dependence of fracture risk. Information regarding the utility in assessing trabecular bone mineral density by quantitative computer tomography (QCT) in these patients, either in the Canaries or in Spain, is lacking. Moreover, in this setting, the importance of secondary hyperparathyroidism is still controversial. DESIGN, PATIENTS AND METHODS Cross-sectional observational study performed on 1177 consecutive Canary postmenopausal women who attended our Bone Metabolic Unit. The Patient Group was composed of 88 postmenopausal women who were taking oral corticosteroids in dose higher than 7.5 mg/day of prednisone or equivalent for more than 6 months (OG group). The Control Group included 838 postmenopausal women who did not take steroids. A complete validated questionnaire for osteoporosis risk assessment and a complete physical examination were performed. A lateral X-ray of the spine was performed on every woman. Bone mineral density (BMD) was measured at the lumbar spine (LS) by dual X-ray Absorptiometry (DXA) and QCT and at the femoral neck by DXA. Fasting serum and 24 hour urine was collected and biochemical markers of bone remodelling were studied. RESULTS Both groups were comparable in general characteristics and calcium intake. The OG group showed lower values of BMD estimated both by DXA and QCT (p<0.05). LS BMD was closely correlated by using both methods (r=0.636, p<0.001). The OG group showed lower values of osteocalcin (p=0.023) and TRAP (p=0.026) without significant differences in PTH. Patients in OG group had a higher prevalence of vertebral fractures than controls (13.3% vs 8.6%; crude values: p=0.049, OR: 1.63 (0.99-2.67); age adjusted: p=0.003, OR 2.29 (1.33-9.93)). CONCLUSIONS In postmenopausal Canarian women, chronic glucocorticoid therapy is associated with low bone mineral density, measured either by DXA or QCT, with evidence of low turnover and high prevalence of fractures without significant changes in PTH. DXA and QCT provide similar information in the assessment of this high risk population.

Beta-blocker use is associated with fragility fractures in postmenopausal women with coronary heart disease

Background and aims: An association between cardiovascular disease and osteoporosis is described. A number of drugs often used by patients with coronary heart disease, such as thiazides, statins and beta-blockers, have shown controversial effects on bone. 1) To study the possible association between coronary heart disease (CHD) and bone mass density (BMD), quantitative ultrasound measurements (QUS) and the prevalence of fragility and vertebral fractures. 2) To study the possible influence of a number of drugs, statins, thiazides and beta-blockers, on BMD and fractures. Methods: Case-control study performed on 74 postmenopausal women who had recently suffered from CHD, and 111 age-matched controls. BMD was measured by Dual X-Ray Absorptiometry (DXA) at the lumbar spine and proximal femur. Quantitative Ultrasound (QUS) was also measured at the heel. Vertebral fractures were diagnosed by lateral, thoracic and lumbar X-rays. The occurrence of non-vertebral fractures was determined by an examination of medical records. Results: Patients with CHD had higher values of BMI. They had a higher prevalence of arterial hypertension and hyperlipidemia, and consequently higher consumption of beta-blockers and statins, but not of thiazides, and had lower alcohol consumption. Patients with CHD had higher BMD values, measured by DXA at the proximal femur, than controls, but there were no differences in DXA values at the lumbar spine or QUS at the heel between the two groups. The prevalence of all fragility factures was slightly higher in patients with CHD, but not to a significant extent. The prevalence of vertebral fractures was similar in the two groups. In a logistic analysis to identify factors associated with all fractures, beta-blockers were positively associated with fragility fractures, and DXA at the femoral neck was inversely associated with fragility fractures. Conclusions: Postmenopausal women with CHD have higher values of BMD at the proximal femur but, despite this, show a slight but nonsignificant increase in the prevalence of fragility fractures. Beta-blockers are independently associated with fragility fractures, but thiazides and statins are not.

Effect of Two Forms of Alendronate Administration upon Bone Mass After Two Years of Treatment

The efficacy of alendronate in slowing the loss of bone mass, or even in increasing it, in osteoporotic patients and thus reducing the risk of new fractures has been described. Nevertheless, the way of taking this drug, together with its side effects, sometimes produces withdrawals. In this study, we analyzed if an alternative way of taking the alendronate improves the follow-up of the treatment and if it had the same effect on bone mineral metabolism than the traditional way of prescription. An open, intention-to-treat study, with follow-up of 2 yr was conducted. Eighty women suffering from postmenopausal osteoporosis were included in the study. They were classified in a random manner into two groups, each one of them received 10 mg/d alendronate, together with 1.2 g of calcium and 800 IU of Vitamin D3. Group I received the drug fasting, before breakfast, as usually prescribed and group II received the alendronate fasting, at noon, before lunch. Biochemical markers of bone remodeling were determined. Total alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine calcium/creatinine ratio, crosslinked N-telopeptides of type I collagen/creatinine ratio, serum calcium, and parathyroid hormone were also determined, and a lateral dorsolumbar radiography of the spine was performed. Bone mineral density was determined in the lumbar spine by dual-energy X-ray absorptiometry and quantitative computed tomography and by dual-energy X-ray absorptiometry in the proximal femur. Both groups showed an increase in bone mineral density in the lumbar spine and in the proximal femur, which was statistically significant after 1 yr of treatment in the range between 1.5% and 4.3%, depending on the anatomical localization where bone mineral density was measured. There was also an important decrease in the biochemical markers of bone remodeling, between 5.6% and 42.5%, depending on the biochemical marker; the decrease of amino-terminal telopetide during the first year was more important. The group that received alendronate in the morning reported a significantly higher number of withdrawals than the group that received the drug at noon. The alternative administration of 10 mg alendronate at noon had the same effect on bone mineral metabolism than its traditional administration in the morning, but the rate of withdrawals was significantly lower.