Estimation of in vivo bone mineral density (BMD) and shape characterization for diagnosing osteoporosis by ultrasonic inspection.

A new method for estimating in vivo bone mineral density (BMD) and characterizing the shape of cancellous bone has been proposed using the results of ultrasonic inspection for the diagnosis of osteoporosis. The method is based on two-dimensional bone area fraction S (percent bone area between bone and bone marrow) calculated from the difference in the speed of ultrasonic wave propagation through cancellous bone. It was shown that the two-dimensional area fraction of a heel bone gives a good relationship to the BMD by DXA (dual energy x-ray absorptiometry) testing of human heel bone (calcaneus) and spine (vertebrae lumbar), as expressed by the relation, BMD (g/cm2) = 0.0167S for heel bone (r = 0.83), and BMD (g/cm2) = 0.0254S + 0.123 for the spine (r = 0.77). Shape characterization is based on the image simulation procedure employing eight random variables from a computer and the statistical results of fractal analysis for numerous cancellous bone patterns. We also demonstrate the validity of the shape characterization using autopsy specimens as a diagnostic tool for osteoporosis.     

Effect of parity on bone mineral density in female rhesus macaques from Cayo Santiago

This cross-sectional study investigates the relationship between parity, bone mineral density, and spontaneous osteopenia/osteoporosis in a large skeletal population of female rhesus macaques (Macaca mulatta) from the free-ranging colony of Cayo Santiago, Puerto Rico. The sample consists of 119 mature female monkeys aged 4.0-22.2 years at time of death. The data consist of measurements of bone mineral content (BMC) and bone mineral density (BMD), obtained from dual-energy X-ray absorptiometry (DEXA) of the last lumbar vertebra. After controlling for age, there is a significant increase in BMD of the spine with increasing parity (P = 0.0006), up to a parity of 7 offspring. Thus, high parity initially has a positive effect on BMD in female rhesus monkeys, but this positive effect disappears with parities that are greater than 7 offspring. After controlling for parity, however, age has a negative (P = 0.015) effect on BMD, beginning several years after the attainment of peak BMD (age 9.5 years). Thus, it appears that parity initially mitigates the effects of aging, but the positive effect of parity on BMD is eventually overwhelmed by the aging process. Mean BMC and BMD values are higher in parous females compared to nulliparous females in the same age range. Similarly, females with low parity have significantly lower mean BMD values than do age-matched high-parity controls, and the frequency of osteopenia and osteoporosis is greater in low-parity females. Forty-three percent (43%) of the osteopenic/osteoporotic females in the sample are members of the low-parity group, even though it composes only 13% (16/119) of the entire sample. This study demonstrates that the free-ranging female rhesus monkeys from Cayo Santiago are a good nonhuman primate model for the study of bone mineral density, parity, osteopenia, and osteoporosis.     

The effects of growth hormone on cortical and cancellous bone

Growth hormone (GH) has profound effects on linear bone growth, bone metabolism and bone mass. The GH receptor is found on the cell surface of osteoblasts and osteoclasts, but not on mature osteocytes. In vitro, GH stimulates proliferation, differentiation and extracellular matrix production in osteoblast-like cell lines. GH also stimulates recruitment and bone resorption activity in osteoclast-like cells. GH promotes autocrine/paracrine insulin-like growth factor 1 (IGF-I) production and endocrine (liver-derived) IGF-I production. Some of the GH-induced effects on bone cells can be blocked by IGF-I antibodies, while others cannot. In animal experiments, GH administration increases bone formation and resorption, and enhances cortical bone mass and mechanical strength. When GH induces linear growth, increased cancellous bone volume is seen, but an unaffected cancellous bone volume is found in the absence of linear growth. Patients with acromegaly have increased bone formation and resorption markers. Bone mass results are conflicting because many acromegalics have hypogonadism, but in acromegalics without hypogonadism, increased bone mineral density (BMD) is seen in predominantly cortical bone, and normal BMD in predominantly cancellous bone. Adult patients with growth hormone deficiency have decreased bone mineral content and BMD. GH therapy rapidly increases bone formation and resorption markers. During the first 6-12 months of therapy, declined or unchanged BMD is found in the femoral neck and lumbar spine. All GH trials with a duration of two years or more show enhanced femoral neck and lumbar spine BMD. In osteoporotic patients, GH treatment quickly increases markers for bone formation and resorption. During the first year of treatment, unchanged or decreased BMD values are found, whereas longer treatment periods report enhanced or unchanged BMD values. However, existing trials comprising relatively few patients and limited treatment periods do not allow final conclusions to be drawn regarding the effects of GH on osteoporosis during long-term treatment.     

Effects of Bisphosphonates on Osteoporosis Induced by Duchenne Muscular Dystrophy: A Prospective Study

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD.Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated.Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group (P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline).Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol.Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid     

Zoledronic Acid Versus Alendronate In The Treatment of Children With Osteogenesis Imperfecta: A 2-Year Clinical Study

Objective: Bisphosphonates have been demonstrated to increase the bone mineral density (BMD) of osteogenesis imperfecta (OI) patients. We aimed to compare the efficacy and safety of intravenous zoledronic acid and oral alendronate in patients with OI.Methods: A total of 161 patients with OI ranging from 2 to 16 years old were included and randomized at a 2:1 ratio to receive either weekly oral alendronate (ALN) 70 mg or a once-yearly infusion of zoledronic acid (ZOL) for 2 years. The primary endpoints were percentage change from baseline in lumbar spine (LS) BMD and change in Z-scores of LS BMD.Results: A total of 136 patients with OI completed the 2-year clinical study, 90 of whom were assigned to receive ALN, while 46 received ZOL treatment. The percentage change in LS BMD was 60.01 ± 7.08% in the ALN group and 62.04 ± 5.9% in the ZOL group (P = .721). The corresponding BMD Z-score increased by 0.50 ± 0.05 in the ALN group and 0.71 ± 0.06 in the ZOL group (P = .013). ZOL was superior to ALN in reducing the clinical fracture rate (hazard ratio, 0.23; 95% confidence interval, 0.118 to 0.431). There was no difference in the incidence of severe side effects between the two groups.Conclusion: A once-yearly 5 mg infusion of ZOL and weekly oral ALN had similar effects in increasing BMD and reducing bone resorption in children and adolescents with OI. ZOL was superior to ALN in reducing the clinical fracture rate.Abbreviations: 25OHD = 25-hydroxyvitamin D; ALN = alendronate; ALP = alkaline phosphatase; β-CTX = cross-linked C-telopeptide of type I collagen; BMD = bone mineral density; BP = bisphosphonate; FN = femoral neck; LS = lumbar spine; OI = osteogenesis imperfecta; SAE = severe adverse event; ZOL = zoledronic acid     

Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment

Introduction

Osteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections.

Methods

Methods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD).

Results

AS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase.

Conclusions

Osteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.     

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm²).ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)     

Variations in mineralization affect the stress and strain distributions in cortical and trabecular bone

The mechanical properties of bone depend largely on its degree and distribution of mineralization. The present study analyzes the effect of an inhomogeneous distribution of mineralization on the stress and strain distributions in the human mandibular condyle during static clenching. A condyle was scanned with a micro-CT scanner to create a finite element model. For every voxel the degree of mineralization (DMB) was determined from the micro-CT scan. The Young's moduli of the elements were calculated from the DMB using constant, linear, and cubic relations, respectively. Stresses, strains, and displacements in cortical and trabecular bone, as well as the condylar deformation (extension along the antero-posterion axis) and compliance were compared. Over 90% of the bone mineral was located in the cortical bone. The DMB showed large variations in both cortical bone (mean: 884, SD: 111 mg/cm(3)) and trabecular bone (mean: 738, SD: 101 mg/cm(3)). Variations of the stresses and the strains were small in cortical bone, but large in trabecular bone. In the cortical bone an inhomogeneous mineral distribution increased the stresses and the strains. In the trabecular bone, however, it decreased the stresses and increased the strains. Furthermore, the condylar compliance remained relatively constant, but the condylar deformation doubled. It was concluded that neglect of the inhomogeneity of the mineral distribution results in a large underestimation of the stresses and strains of possibly more than 50%. The stiffness of trabecular bone strongly influences the condylar deformation. Vice versa, the condylar deformation largely determines the magnitude of the strains in the trabecular bone.     

Genetic and environmental correlations between bone mineral density and bone size in Caucasians

To explore the magnitude of common genetic and environmental effects shared by bone mineral density (BMD) and bone size (BS) in a large sample of 4,489 subjects (2,667 females and 1,822 males) from 582 Caucasian pedigrees, we performed a bivariate variance decomposition analysis to evaluate genetic correlation (rhoG), environmental correlation (rhoE), and phenotypic correlation (rhoP) between BMD and BS at the spine and hip, as well as their "synthesized" skeletal site (bone mineral density principal component, bone size principal component) generated by principal components analysis. Significant rhoG, rhoE, and rhoP were detected, but the shared genetic influence on BMD and BS was only 21%, 1.3%, and 11.6% at the spine, hip, and their joint variable, respectively. The results suggest that it may be important to choose both BMD and BS, especially at the hip, as surrogate phenotypes for osteoporosis genetic studies in Caucasians.     

Alendronate increases bone mineral density in patients with symptomatic primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is often associated with low bone mineral density (BMD). An open-labeled, prospective trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with advanced PHPT. All patients had symptomatic PHPT and met surgical guidelines however refused surgery. Nineteen patients was treated with alendronate for 2 years. The primary outcome index, BMD, was measured at the lumbar spine (LS) and femoral neck (FN) every 6 months by dual-energy x-ray absorptiometry. Serum calcium, phosphorous and PTH, and urinary calcium excretion were monitored every 3 months. Treatment with alendronate over 2 years was associated with a significant (5.3+/-0.4%; p<0.01) increase in LS BMD in comparison with baseline. FN BMD increased significantly at 24 months with alendronate by 2.5%+/-0.7 (p<0.01) from baseline. Serum calcium, phosphorus and PTH, and urine calcium excretion did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS and FN at 24 months from baseline values with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in symptomatic PHPT among those with low BMD, who are candidates for surgery but either decline or for whom surgery is contraindicated.     

Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution

The bone remodeling process takes place at the surface of trabeculae and results in a non-uniform mineral distribution. This will affect the mechanical properties of cancellous bone, because the properties of bone tissue depend on its mineral content. We investigated how large this effect is by simulating several non-uniform mineral distributions in 3D finite element models of human trabecular bone and calculating the apparent stiffness of these models. In the ‘linear model’ we assumed a linear relation between mineral content and Young's modulus of the tissue. In the ‘exponential model’ we included an empirical exponential relation in the model. When the linear model was used the mineral distribution slightly changed the apparent stiffness, the difference varied between an 8% decrease and a 4% increase compared to the uniform model with the same BMD. The exponential model resulted in up to 20% increased apparent stiffness in the main load-bearing direction. A thin less mineralized surface layer (28 μm) and highly mineralized interstitial bone (mimicking mineralization resulting from anti-resorptive treatment) resulted in the highest stiffness. This could explain large reductions in fracture risk resulting from small increases in BMD. The non-uniform mineral distribution could also explain why bone tissue stiffness determined using nano-indentation is usually higher than finite element (FE)-determined stiffness. We conclude that the non-uniform mineral distribution in trabeculae does affect the mechanical properties of cancellous bone and that the tissue stiffness determined using FE-modeling could be improved by including detailed information about mineral distribution in trabeculae in the models.     

Determination of the relationship between collagen cross-links and the bone-tissue stiffness in the porcine mandibular condyle

Although bone-tissue stiffness is closely related to the degree to which bone has been mineralized, other determinants are yet to be identified. We, therefore, examined the extent to which the mineralization degree, collagen, and its cross-links are related to bone-tissue stiffness. A total of 50 cancellous and cortical bone samples were derived from the right mandibular condyles of five young and five adult female pigs. The degree of mineralization of bone (DMB) was assessed using micro-computed tomography. Using high-performance liquid chromatography, we quantified the collagen content and the number of cross-links per collagen molecule of two enzymatic cross-links: hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), and one non-enzymatic cross-link: pentosidine (Pen). Nanoindentation was used to assess bone-tissue stiffness in three directions, and multiple linear regressions were used to calculate the correlation between collagen properties and bone-tissue stiffness, with the DMB as first predictor. Whereas the bone-tissue stiffness of cancellous bone did not differ between the three directions of nanoindentation, or between the two age groups, cortical bone-tissue stiffness was higher in the adult tissue. After correction for DMB, the cross-links studied did not increase the explained variance. In the young group, however, LP significantly improved the explained variance in bone-tissue stiffness. Approximately half of the variation in bone-tissue stiffness in cancellous and cortical bone was explained by the DMB and the LP cross-links and thus they cannot be considered the sole determinants of the bone-tissue stiffness.     

Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual-energy X-ray absorptiometry technique

doi: 10.1111/j.1741‐2358.2012.00625.x Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual‐energy X‐ray absorptiometry technique Objective: The aim of this study was to compare the mandibular body bone mineral density according to bone mineral density status of spine and femur measured by dual‐energy X‐ray absorptiometry (DXA) technique in elderly edentulous individuals. Background: One of the factors that affect the survival rate of implants is bone mineral density (BMD) of the jaws. Materials and methods: Fifty edentulous elderly patients’ (27 women and 23 men) spine, femur and the mandibular body BMDs were measured using DXA technique. BMD scans of the AP lumbar spine (L2–L3) and femur were classified using World Health Organisation criteria for bone mass. Results: There was a statistically significant difference between the normal femur group’s–osteoporosis group’s mandibular body BMD (p = 0.001) and femoral osteopaenia group’s–osteoporosis group’s mandibular body BMD (p < 0.001). The femoral osteoporosis group’s mandibular body BMDs were lower than those of both the normal femoral and the femoral osteopaenia group subjects’. Conclusion: Classification of edentulous mandibles according to low and high bone mineral densities is a problem in implant dentistry. The results of this study demonstrated that femoral bone mineral density status may be used to provide preliminary information about the bone mineral density of the mandibular body region in elderly edentulous subjects.     

Bone mineral density, osteopenia, and osteoporosis in the rhesus macaques of Cayo Santiago

This cross-sectional study investigates metabolic bone disease and the relationship between age and bone mineral density (BMD) in males and females of a large, well-documented skeletal population of free-ranging rhesus monkeys (Macaca mulatta), from the Caribbean Primate Research Center Museum collection from Cayo Santiago, Puerto Rico. The sample consists of 254 individuals aged 1.0-20+ years. The data consist of measurements of bone mineral content and bone mineral density, obtained from dual-energy X-ray absorptiometry (DEXA), of the last lumbar vertebra from each monkey. The pattern of BMD differs between male and female rhesus macaques. Females exhibit an initial increase in BMD with age, with peak bone density occurring around age 9.5 years, and remaining constant until 17.2 years, after which there is a steady decline in BMD. Males acquire bone mass at a faster rate, and attain a higher peak BMD at an earlier age than do females, at around 7 years of age, and BMD remains relatively constant between ages 7-18.5 years. After age 7 there is no apparent effect of age on BMD in the males of this sample; males older than 18.5 years were excluded due to the presence of vertebral osteophytosis, which interferes with DEXA. The combined frequency of osteopenia and osteoporosis in this population is 12.4%. BMD values of monkeys with vertebral wedge fractures are generally higher than those of virtually all of the nonfractured osteopenic/osteoporotic individuals, thus supporting the view that BMD as measured by DEXA is a useful but imperfect predictor of fracture risk, and that low BMD may not always precede fractures in vertebral bones. Other factors such as bone quality (i.e., trabecular connectivity) should also be considered. The skeletal integrity of a vertebra may be compromised by the loss of key trabeculae, resulting in structural failure, but the spine may still show a BMD value within normal limits, or within the range of osteopenia.     

Association between estrogen receptor alpha gene polymorphisms and bone mineral density in Polish female patients with Graves' disease

Graves' (GD) hyperthyroidism leads to reduced bone mineral density (BMD) accompanied by accelerated bone turnover. Ample studies have identified association between estrogen receptor (ESR1) gene polymorphism and decreased BMD and osteoporosis. In contrast, number of publications that link ESR1, BMD and Graves' disease is limited. The purpose of this study was to identify the association between ESR1 polymorphisms and BMD in premenopausal women with GD and to determine whether ESR1 polymorphic variants can predispose to GD. The study included 75 women aged 23-46 years with GD and 163 healthy controls. BMD was measured at lumbar spine and femoral neck. We investigated two SNPs in the ESR1 gene and analyzed genetic variants in the form of haplotypes reconstructed by statistical method. Three out of four possible haplotypes of the PvuII and XbaI restriction fragment length polymorphisms were found in GD patients: px (55.3 %), PX (33.3 %) and Px (11.4 %). Women homozygous for xx of XbaI and for pp of PvuII had the lowest BMD at lumbar spine. Moreover, the px haplotype predisposed to reduced lumbar BMD. No associations were observed for femoral neck BMD. No statistically significant relationship were found between ESR1 polymorphisms or their haplotypes and GD. These results indicate that the PvuII and the XbaI polymorphisms of ESR1 gene are associated with bone mineral density in premenopausal women with GD and may help to estimate the risk of bone loss particularly at lumbar spine. However, none of the ESR1 gene alleles predict the risk of GD in Polish female patients.     

Parathyroid hormone gene with bone phenotypes in Chinese

Osteoporosis is a common disorder afflicting old people. The parathyroid hormone (PTH) gene is involved in bone remodeling and calcium homeostasis, and has been considered as an important candidate gene for osteoporosis. In this study, we simultaneously tested linkage and/or association of PTH gene with bone mineral density (BMD) and bone mineral content (BMC), two important risk factors for osteoporosis. A sample of 1263 subjects from 402 Chinese nuclear families was used. The families are composed of both parents and at least one healthy daughter aged from 20 to 45 years. All the subjects were genotyped at the polymorphic BstBI site inside the intron 2 of the PTH gene (a nucleotide substitution of G to A at the position +3244). BMD and BMC were measured at the lumbar spine and the hip region via dual-energy X-ray absorptiometry (DXA). Using QTDT (quantitative trait transmission disequilibrium test), we did not find significant results for association or linkage between the PTH gene and BMD or BMC variation at the spine or hip. Our data do not support the PTH gene as a quantitative trait locus (QTL) underlying the bone phenotypic variation in the Chinese population.     

No major effect of estrogen receptor beta gene RsaI polymorphism on bone mineral density and response to alendronate therapy in postmenopausal osteoporosis

Genetic factors play an important role in the pathogenesis of osteoporosis. The genes involved are, however, still largely unknown. In the present study, we have investigated whether sequence variations in the estrogen receptor beta (ERbeta) gene are associated with bone mineral density (BMD) and biochemical markers of bone turnover in 79 Slovenian postmenopausal women with osteoporosis. We also assessed the response by BMD and bone markers to antiresorptive therapy with bisphosphonate alendronate. All eight exons of ERbeta gene were amplified by polymerase chain reaction and screened for mutations by single-strand conformation polymorphism analysis. Potentially mutated samples were found only in exon 5 and sequence analysis identified the presence of a silent mutation in codon 328 with a nucleotide substitution GTG to GTA. For easier detection of this silent mutation, the RsaI restriction fragment length polymorphism analysis was developed. The frequencies of genotypes were as follows: Rr 5.1% and RR 94.9%. Between both genotypes, no significant differences in baseline lumbar spine and femoral neck BMD or in bone markers osteocalcin and deoxypyridinoline were observed. Similarly, no significant difference between RR and Rr genotypes in BMD or bone markers after 1 year of therapy was found. The increase in lumbar spine BMD after therapy was the only parameter that approached statistical significance (P=0.099). Patients with genotype Rr showed a smaller increase compared to those with RR. Our results suggest that RsaI polymorphism of ERbeta gene is probably not an important genetic determinant of BMD and does not significantly influence the responsiveness to alendronate therapy.     

Prevalence of Osteoporosis in Ambulatory Postmenopausal Women from A Semiurban Region in Southern India: Relationship to Calcium Nutrition and Vitamin D Status

ObjectiveTo assess the prevalence of osteoporosis in healthy ambulatory postmenopausal Indian women as measured by dual-energy x-ray absorptiometry and to study the dietary calcium intake and vitamin D status and their influence on bone mineral density (BMD).MethodsWe conducted a community-based crosssectional study in a semiurban region. A randomized cluster sampling technique was used. The study cohort consisted of 150 ambulatory postmenopausal women (≥ 50 years old). Dual-energy x-ray absorptiometry for BMD was performed at the lumbar spine and femoral neck. Dietary calcium intake and biochemical variables were assessed.ResultsThe prevalence of osteoporosis was 48% at the lumbar spine, 16.7% at the femoral neck, and 50% at any site. The mean dietary calcium intake was much lower than the recommended intake for this age-group. There was a significant positive correlation between body mass index and BMD at the lumbar spine and the femoral neck (r = 0.4; P = .0001). BMD at the femoral neck was significantly less (mean, 0.657 versus 0.694 g/cm²) in the vitamin D-insufficient study subjects in comparison with the vitamin D-sufficient women (P = .03).ConclusionThe high prevalence of osteoporosis and vitamin D insufficiency in this semiurban group of postmenopausal women in India is a major health concern. Measures such as adequate calcium intake and vitamin D supplementation in women of this age-group may be beneficial. (Endocr Pract. 2008;14:665-671)     

Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.

OBJECTIVE--To evaluate the need for a randomised study of treatment of spinal osteoporosis with human parathyroid peptide in the secondary prevention of crush fractures; to study the effect of human parathyroid hormone peptide 1-34 plus sex hormones on vertebral body cancellous bone; and, separately, to determine the effect of relatively low doses of sodium fluoride plus calcium on spinal bone mineral density. DESIGN--Open study of patients with primary or postmenopausal osteoporosis. All patients had serial bone densitometry of the spine by quantitative computed tomography and dual photon absorptiometry as well as serial densitometry of the radial midshaft (cortical) and radial distal (trabecular) bone by quantitative computed tomography. Changes in the spinal bone not forming the spongiosa of the vertebral bodies ("cortical" bone) were determined from the difference between the two axial measurements, after correction to the same units of measurement. SETTING--Northwick Park Hospital and Medical Research Council Clinical Research Centre. PATIENTS--24 Patients who fulfilled the conventional criteria for type 1 (vertebral) osteoporosis not secondary to recognised causes other than sex hormone deficiency and with at least one crush or wedge vertebral fracture and a spinal bone density (quantitative computed tomography) less than 80 mg/cm3 or two or more fractures. Twelve patients received human parathyroid peptide and 12 sodium fluoride; they were not randomised. MAIN OUTCOME MEASURES--Trends in axial and peripheral bone mass values determined by linear, time dependent regression analyses. RESULTS--The patients receiving the peptide showed a substantial increase in vertebral spongiosa (mean 25.6 mg/cm2 two years after the start of treatment). No significant changes were seen in spinal cortical or radial bone density. The patients receiving sodium fluoride showed roughly equal increases in cancellous and cortical bone over the same period (mean increase in vertebral spongiosa 16.1 mg/cm3). No significant changes were seen in radial bone. CONCLUSIONS--Treatment of postmenopausal women with human parathyroid peptide selectively increases spinal cancellous bone density by amounts that may prove useful in secondary prevention. Peptide treatment should now be tested in a randomised study in which the important end point is prevention of fractures as the usefulness of sodium fluoride in this context is doubtful.     

Bone mineral density and body composition in men with multiple sclerosis chronically treated with low-dose glucocorticoids

The aim of the study was to compare the bone mineral density (BMD) and body composition between ambulatory male MS patients and control subjects and to evaluate the relationships among body composition, motor disability, glucocorticoids (GC) use, and bone health. Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age: 45.2 years) chronically treated with low-dose GC and in 54 healthy age-matched men. Compared to age-matched controls, MS patients had a significantly lower total body bone mineral content (TBBMC) and BMD at all measured sites except for the radius. Sixty five male MS patients (62.5 %) met the criteria for osteopenia and twenty six of them (25 %) for osteoporosis. The multivariate analysis showed a consistent dependence of bone measures (except whole body BMD) on BMI. The total leg lean mass % was as an independent predictor of TBBMC. The Expanded Disability Status Scale (EDSS), cumulative GC dose and age were independent determinants for BMD of the proximal femur. We conclude that decreasing mobility in male MS patients is associated with an increasing degree of osteoporosis and muscle wasting in the lower extremities. The chronic low-dose GC treatment further contributes to bone loss.