Cortical BMC Research Articles

Obesity alters cortical and trabecular bone density and geometry in women

The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone using quantitative computed tomography. A higher body mass index (BMI) was positively associated with trabecular and cortical bone parameters, and serum parathyroid hormone, and negatively associated with cortical volumetric bone mineral density (vBMD) and serum 25-hydroxy-vitamin D. When BMI is greater than 35 kg/m(2), adiposity affects vBMD and may explain the higher fracture risk in this population without low BMD. The influence of adult obesity on the trabecular and cortical bone, geometry, and strength has not been fully addressed. The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone mass and geometry, over a wide range of body weights. We examined 211 women (25-71 years; BMI 18-57 kg/m(2)) who were classified into three categories of BMI (kg/m(2)) including normal-weight (BMI<25), overweight and obese-class I (BMI 25-35) and obese-class II-III (BMI>35), and also by menopausal status. Volumetric bone mineral density (mg/cm(3)), trabecular, and cortical components as well as geometric characteristics at the 4%, 38%, and 66% from the distal tibia were measured by peripheral quantitative computed tomography, and serum was analyzed for parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD). Higher BMI was associated with greater values of trabecular bone and cortical BMC and area and PTH (r>0.39, p<0.001), but lower cortical vBMD and 25OHD (r>-0.27, p<0.001). When controlling for lower leg muscle area, fat area was inversely associated with cortical vBMD (r=-0.16, p<0.05). Premenopausal obese women with both higher BMI and PTH had lower cortical vBMD (r<-0.40, p<0.001). While age is a predictor for most bone variables, fat mass explains more variance for vBMD, and lean mass and 25OHD explain greater variance in geometric and strength indices (p<0.05). Severe obesity (BMI>35) increases trabecular vBMD and in the presence of a higher PTH is associated with a lower cortical vBMD without compromising bone geometry and strength. Whether or not a lower cortical vBMD in obesity influences fracture risk over time needs to be further explored.

Adiponectin and its association with bone mass accrual in childhood

Circulating adiponectin levels are inversely related to bone mineral density (BMD) in humans and animal models. Previous studies in humans have been confined largely to adult populations, and whether adiponectin influences bone mass accrual in childhood is unclear. We examined this question using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort by investigating relationships between circulating adiponectin levels at a mean age of 9.9 years, indices of bone mass as measured by total-body dual-energy X-ray absorptiometry (DXA) at ages 9.9 and 15.5 years, and cortical bone parameters as measured by peripheral quantitative computed tomography (pQCT) of the midtibia at age 15.5 years. A total of 4927 children were included at age 9.9 years, of whom 97% and 90% of boys and girls, respectively, were in prepuberty or early puberty, as defined by Tanner stage 1-2. A total of 2754 children were included at age 15.5 years, of whom 95% and 97% of boys and girls, respectively, were in late puberty, as defined by Tanner stage 4-5. Circulating adiponectin was found to be related to fat mass, lean mass, and, to a lesser extent, height, so analyses were adjusted for these three variables to identify possible independent effects of adiponectin on bone development. Adiponectin was inversely related to total-body-less-head bone mineral content (BMC; -3.0%), bone area (BA; -1.8%), BMC divided by BA (BMD; -4.8%), and BMC adjusted for BA by linear regression (aBMC; -5.6%), as measured at age 9.9 years (coefficients show change per doubling in adiponectin concentration, p < .001). Consistent with these results, inverse associations also were seen between adiponectin and cortical BMC (-4.8%) and cortical bone area (-4.7%), as measured by tibial pQCT at age 15.5 years (p < .001). Further pQCT results suggested that this inverse association of adiponectin with skeletal development predominantly involved a negative association with endosteal relative to periosteal expansion, as reflected by cortical thickness (-6.0%, p < .001). We conclude that, independent of fat mass, lean mass, and height, adiponectin is associated with lower bone mass in childhood predominantly owing to an influence on relative endosteal expansion. Since these associations were observed before and after puberty, this suggests that setting of adiponectin levels in midchildhood has the potential to exert long-term effects on bone strength and fracture risk.

Skeletal Benefits After Long-Term Retirement in Former Elite Female Gymnasts

Bone strength benefits after long-term retirement from elite gymnastics in terms of bone geometry and volumetric BMD were studied by comparing retired female gymnasts to moderately active age-matched women. In a cross-sectional study, 30 retired female gymnasts were compared with 30 age-matched moderately active controls. Bone geometric and densitometric parameters were measured by pQCT at the distal epiphyses and shafts of the tibia, femur, radius, and humerus. Muscle cross-sectional areas were assessed from the shaft scans. Independent t-tests were conducted on bone and muscle variables to detect differences between the two groups. The gymnasts had retired for a mean of 6.1 +/- 0.4 yr and were engaged in <or=2 h of exercise per week since retirement. At the radial and humeral shafts, cortical cross-sectional area (CSA), total CSA, BMC, and strength strain index (SSIpol) were significantly greater (13-38%, p <or= 0.01) in the retired gymnasts; likewise, BMC and total CSA were significantly greater at the distal radius (22-25%, p <or= 0.0001). In the lower limbs, total CSA and BMC at the femur and tibia shaft were greater by 8-11%, and trabecular BMD and BMC were only greater at the tibia (7-8%). Muscle CSA at the forearm and upper arm was greater by 15-17.6% (p <or= 0.001) but was not different at the upper and lower leg. Past gymnastics training is associated with greater bone mass and bone size in women 6 yr after retirement. Skeletal benefits were site specific, with greater geometric adaptations (greater bone size) in the upper compared with the lower limbs.

Genetic Regulation of Bone Traits Is Influenced by Sex and Reciprocal Cross in F2 Progeny From GK and F344 Rats

A genome-wide linkage analysis to identify quantitative trait loci (QTLs) for bone phenotypes was performed in an F(2) intercross of inbred spontaneously type 2 diabetic GK and normoglycemic F344 rats (108 males and 98 females). The aim of the study was to locate genome regions with candidate genes affecting trabecular and cortical bone and to investigate the effects of sex and reciprocal cross. pQCT was used to determine tibial bone phenotypes in the F(2) rats, comprising reciprocal crosses with divergent mitochondrial (mt) DNA. Sex and reciprocal cross-separated QTL analyses were performed followed by assessment of specific interactions. Four genome-wide significant QTLs linked to either cortical vBMD, tibia length, body length, or metaphyseal area were identified in males on chromosomes (chr) 1, 8, and 15. In females, three significant QTLs linked to cortical BMC or metaphyseal total vBMD were identified on chr 1 and 2. Several additional suggestive loci for trabecular and cortical traits were detected in both males and females. Four female-specific QTLs on chr 2, 3, 5, and 10 and four reciprocal cross-specific QTLs on chr 1, 10, and 18 were identified, suggesting that both sex and mt genotype influence the expression of bone phenotypes.

Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry

Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of approximately 8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) > or =0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF > or = 0.05) variation in the region with r (2) > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men > or =40 yr of age. Association analysis showed three SNPs in a 3' region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p < or = 0.006), and in 416 individuals > or =18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry.

Reanalysis precision of 3D quantitative computed tomography (QCT) of the spine

PurposeTo evaluate the precision of 3D QCT of the spine. MethodsInteroperator analysis reproducibility of two different 3D QCT analysis systems (QCTPro from Mindways Software Inc and MIAF-Spine from the Institute of Medical Physics, University of Erlangen) was evaluated in 29 postmenopausal women. For each analysis system four different trained operators analyzed all scans independently. Results of the vertebrae L1 and L2 were averaged. With QCTPro BMD of the central trabecular elliptical VOI was analyzed. With MIAF-Spine integral, trabecular and cortical BMD, BMC and volume were analyzed in the total vertebral body, the elliptical cylinder and the Osteo VOIs that were further subdivided into superior, mid and inferior subVOIs, each. ResultsPrecision errors (%CVrms) for the central trabecular VOI that is also used in the traditional single slice QCT techniques were 1.7±2.2% and 0.6±0.6% for QCTPro and MIAF-Spine, respectively. For MIAF-Spine integral BMD precision errors were lowest in the total and mid Osteo subVOIs (0.5±0.5%). Trabecular BMD precision errors were lowest in the mid subVOIs (0.6±0.6%). For trabecular BMD there were no differences among the total vertebral body, elliptical cylinder and Osteo VOIs. Cortical BMD precision errors were lowest in the mid total vertebral body subVOI (2.1±1.9%) and slightly higher in the mid of the Osteo subVOI. Precision errors in the superior and inferior subVOIs were typically 50% to 100% higher compared to the mid subVOIs. DiscussionCompared to QCTPro MIAF-Spine uses an automated 3D segmentation and an anatomic vertebral coordinate system to position a variety of analysis VOIs. This results in better precision than the more manually assisted analysis used by QCTPro. In-vivo precision errors will be approximately 0.5% higher compared to the analysis precision errors reported here (13). The results demonstrate that with 3D QCT in-vivo precision errors of about 1%-1.5% for trabecular and 2.5% to 3% for cortical bone can be obtained in postmenopausal women.

Hyperlipidemia Impairs Osteoanabolic Effects of PTH

Epidemiological and in vitro studies have suggested that hyperlipidemia/oxidized phospholipids adversely affect bone. We recently found that oxidized phospholipids attenuate PTH-induced cAMP and immediate-early gene (IEG) expression in MC3T3-E1 cells, raising concerns that clinical hyperlipidemia may attenuate osteoanabolic effects of PTH in vivo. Thus, we studied whether intermittent PTH treatment has differential osteoanabolic effects in wildtype (C57BL/6) and hyperlipidemic (LDLR(-/-)) mice. Consistent with our previous in vitro studies, induction of IEGs in calvarial tissue, 45 min after a single dose of recombinant hPTH(1-34), was attenuated in LDLR(-/-) mice compared with C57BL/6 mice. Daily hPTH(1-34) injections for 5 wk significantly increased total and cortical BMD and BMC, assessed by pQCT, in C57BL/6 mice. However, this induction was completely abrogated in LDLR(-/-) mice. Similarly, PTH(1-34) failed to increase BMD in another hyperlipidemic mouse model, ApoE(-/-) mice. Histomorphometric analysis showed that trabecular bone of both mice responded similarly to PTH(1-34). Structural parameters improved significantly in response to PTH(1-34) in both mouse strains, although to a lesser degree in LDLR(-/-) mice. With PTH(1-34) treatment, osteoblast surface trended toward an increase in C57BL/6 mice and increased significantly in LDLR(-/-) mice. PTH(1-34) did not alter resorption parameters significantly, except for the eroded surface (ES/BS), which was reduced in the C57BL/6 but not in the LDLR(-/-) mice. These results show that PTH(1-34) has adverse effects on cortical bones of the hyperlipidemic mice, suggesting that the therapeutic effects of PTH may be compromised in the presence of hyperlipidemia.

IGF-1 and IGF-Binding Proteins and Bone Mass, Geometry, and Strength: Relation to Metabolic Control in Adolescent Girls With Type 1 Diabetes

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12–15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA1c), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r2 = 0.21) and greater IGFBP-1 (r2 = 0.39), IGFBP-5 (r2 = 0.38), and bone-specific alkaline phosphatase (BALP; r2 = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r2 = 0.44–0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r2 ≥ 0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Body mass index (BMI) and serum parathyroid hormone (sPTH) influence cortical bone in premenopausal women

Continuous endogenous sPTH excess has been shown to have catabolic effects on trabecular and cortical bone in normal‐weight women. In this study we examined the relationship between sPTH levels and BMI on cortical and trabecular volumetric bone mineral density (vBMD) and geometry in 87 normocalcemic obese and non‐obese women. Measurements were made by peripheral quantitative computed tomography at 4% and 38% from the distal tibia. In 43 premenopausal women, we used the median to categorize sPTH (pg/mL) as higher (70 ± 24) and lower (29 ± 4), and categorized BMI (kg/m2) into obese (39 ± 9) and non‐obese (26.5 ± 1.8). A similar analysis was performed for a postmenopausal population. Not surprisingly, we found that obesity increased cortical vBMD and content (BMC), geometric properties (area, thickness, circumference), polar moment of inertia and the stress:strain index in all women (P &lt; 0.05), and also increased trabecular vBMD and BMC (P &lt; 0.02) in the premenopausal women. We found an interaction (2‐way ANOVA) between BMI and sPTH for cortical BMC and geometric variables (p &lt; 0.05) in the premenopausal women. Hence, the positive influence of BMI on cortical bone geometric properties is dependent on higher sPTH in the younger women. These findings suggest that the altered hormonal milieu associated with obesity is an important determinant in modulating the effects of excess weight on the skeleton.

Knee loading accelerates bone healing in mice.

Knee loading is an anabolic loading modality that applies lateral loads to the knee. This study shows that loads applied to the proximal tibial epiphysis stimulate healing of surgically generated wounds in the tibial diaphysis. Wound healing is sensitive to mechanical stimulation such as various forms of stress and different magnitudes of strain. Knee loading has been shown to induce anabolic responses to murine tibias and femora when a strain of 10-20 mustrain is applied at the site of new bone formation. The object of this study was to address a question: does knee loading accelerate closure of open wounds in the tibia? Fifty-three C57/BL/6 female mice were used. A surgical wound (0.5 mm in diameter) was generated in the left tibia (loaded) and the right tibia (sham-loaded control). From the fourth postoperative day, knee loading was performed to the left knee with a custom-made piezoelectric loader for 3 min/d for 3 consecutive days. The peak-to-peak force was 0.5 N. Animals were killed 1, 2, or 3 wk after surgery, and the healing process was evaluated with muCT, pQCT, and bone histomorphometry with calcein labeling. The measured strain was <20 mustrain with 0.5-N force regardless of the presence or absence of surgical wounds. Compared with sham-loaded controls, the results showed load-driven acceleration of wound healing. First, muCT data revealed that knee loading reduced the size of surgical wounds by 13% (p < 0.01; 1 wk), 25% (p < 0.001; 2 wk), and 15% (p < 0.01; 3 wk). Second, pQCT data indicated that total BMD and BMC and cortical BMD and BMC were significantly increased in the third postoperative week. Last, bone histomorphometry revealed that bone formation was stimulated from the site proximal (close to the knee) to the wound. The reparative and remodeling phases of wound healing were enhanced by loads applied to the knee without inducing significant in situ strain at the site of wounds. Noninvasive knee loading might therefore be useful clinically to stimulate bone healing in the entire tibia along its length (including cast immobilized wounds).

The RANKL inhibitor OPG-Fc increases cortical and trabecular bone mass in young gonad-intact cynomolgus monkeys

Weekly treatment of gonad-intact cynomolgus monkeys (for up to 6 months) with the RANKL inhibitor OPG-Fc reduced bone turnover markers and increased volumetric cortical and trabecular BMD and BMC at radial and tibial metaphyses. OPG-Fc was well tolerated in this study without evidence of change in measured toxicologic parameters vs. control. RANKL is the primary mediator of osteoclast formation, function, and survival. The catabolic effects of RANKL are inhibited by OPG, a soluble decoy receptor for RANKL. We investigated the safety and pharmacology of OPG-Fc in gonad-intact cynomolgus monkeys. Males and females were treated weekly with vehicle (n = 5/sex) or OPG-Fc (15 mg/kg) by s.c. (n = 5/sex) or i.v. (n = 3/sex) injection for 6 months. Routine toxicologic investigations, hematologic parameters, body and organ weights, and ophthalmologic and electrocardiographic findings were not affected by OPG-Fc treatment. Because s.c. and i.v. dosing of OPG-Fc caused similar effects, these groups were combined for analyses. The following endpoints were significantly different in males and/or females treated with OPG-Fc relative to sex-matched vehicle controls after 6 months (p < 0.05). Biochemical markers of bone turnover (urine N-telopeptide and serum osteocalcin) were significantly decreased with OPG-Fc treatment. Cortical and trabecular volumetric BMD and BMC, cortical thickness, and cross-sectional moment of inertia were significantly increased by OPG-Fc treatment at the proximal tibia and distal radius metaphyses. Increases in cortical thickness were associated with significantly greater periosteal circumference. OPG-Fc increased cortical and trabecular BMD and BMC in young gonad-intact cynomolgus monkeys.

Investigation of central versus peripheral effects of estradiol in ovariectomized mice

It is generally believed that estrogens exert their bone sparing effects directly on the cells within the bone compartment. The aim of the present study was to investigate if central mechanisms might be involved in the bone sparing effect of estrogens. The dose-response of central (i.c.v) 17beta-estradiol (E2) administration was compared with that of peripheral (s.c.) administration in ovariectomized (ovx) mice. The dose-response curves for central and peripheral E2 administration did not differ for any of the studied estrogen-responsive tissues, indicating that these effects were mainly peripheral. In addition, ovx mice were treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780. ICI 182,780 attenuated most of the estrogenic response regarding uterus weight, retroperitoneal fat weight, cortical BMC and trabecular bone mineral content (P<0.05). These findings support the notion that the primary target tissue that mediates the effect of E2 on bone is peripheral and not central.

Growth Hormone Injections Improve Bone Quality in a Mouse Model of Osteogenesis Imperfecta

Systemic growth hormone injections increased spine and femur length in a mouse model of OI. Femur BMC, cross-sectional area, and BMD were increased. Smaller gains were produced in vertebral BMC and cross-sectional area. Biomechanical testing showed improvements to structural and material properties in the femur midshaft, supporting expanded testing of growth hormone therapy in children with OI. Osteoblasts in heterozygous Cola2oim mutant mice produce one-half the normal amounts of the alpha2 strand of type I procollagen. The mice experience a mild osteogenesis imperfecta (OI) phenotype, with femurs and vertebrae that require less force than normal to break in a biomechanical test. Subcutaneous injections of recombinant human growth hormone (rhGH) or saline were given 6 days per week to oim/+ mice between 3 and 12 weeks of age, in a protocol designed to simulate a trial on OI children. rhGH injections promoted significant weight gain and skeletal growth compared with saline-treated control animals. Femur and spine lengths were increased significantly. Significant increases at the femur midshaft in cortical BMD (2.2%), BMC (15.5%), and cross-sectional area (13%) were produced by rhGH treatment. Increases in the same cortical bone parameters were measured in the metaphyseal region of the femur and in tail vertebrae, but lumbar vertebrae showed significant increases in BMC (9.6%) and cross-sectional area (10.1%) of trabecular bone. Three-point bending testing documented functional improvements to the femur mid-shafts. GH treatment produced significant increases in bone stiffness (23.7%), maximum load (30.8%), the energy absorbed by the femurs to the point of maximum load (44.5%), and the energy to actual fracture (40.4%). The ultimate stress endured by the bone material was increased by 14.1%. Gains in bone length, cross-sectional area, BMD, BMC, structural biomechanical properties, and strength were achieved without directly addressing the genetic collagen defect in the mice. Results support expanded clinical testing of GH injections in children with OI.

Assessment of the skeletal status by peripheral quantitative computed tomography of the forearm: Short-term precision in vivo and comparison to dual X-ray absorptiometry

In order to assess precision of peripheral quantitative computed tomography (pQCT), duplicate bone mineral density (BMD) measurements at the radius were performed in 20 healthy premenopausal, 20 healthy postmenopausal, and 20 osteoporotic postmenopausal women using a Stratec XCT-960 system. The short-term reproductibility in vivo for the total, trabecular, and cortical regions of interest (ROI) was expressed as the absolute precision error (standard deviation, SD) and as the relative precision error (SD/mean x 100, or coefficient of variation, CV, in %). Reproducibility in vivo was good in all volunteers but was influenced by the study group and the ROI. The precision error for trabecular BMD was 3 mg/cm3, or about 1.6%. This is large relative to the aging decrease of 0.22%/year, or to the difference (12 mg/cm3, or 7%) between osteoporotic women and postmenopausal controls. In order to compare pQCT to dual X-ray absorptiometry (DXA) at the forearm and at the lumbar spine (L1-L4), 40 premenopausal healthy controls, 40 postmenopausal healthy controls, and 35 postmenopausal osteoporotic women were assessed. DXA measurements performed at the ultradistal, middistal, 1/3, and total ROI of the radius showed only moderate correlations between r = 0.38--0.75, r = 0.27--0.64, and r = 0.38--0.53 for the comparison versus pQCT total BMD, versus pQCT trabecular BMD, and versus pQCT cortical BMD, respectively. Correlations of DXA at the lumbar spine and pQCT were between r = 0.18 and 0.44. DXA at radius and spine was able to discriminate between post- menopausal controls and osteoporotic women (p = 0.001--.004),but BMD measurements by pQCT did not show this ability (p = 0.15--0.52). However, two nonstandard pQCT parameters, namely the surface area of the cortical bone and the cortical BMC were factors that discriminated well between these two groups (p = 0.002, p = 0.005, respectively). These pQCT parameters also yielded the highest relative annual changes in pre- and post-menopausal control subjects. The measurement of cortical bone in the distal radius proved to be a good predictor of vertebral fracture status and was a good indicator of age-related skeletal change. Our data emphasize the importance of cortical measurements when using pQCT of the radius to assess osteoporosis.

CHANGES IN BONE MINERAL, CONTENT (BMC) IN PREPUBERTAL, CHILDREN WITH MARKED SHORT STATHRE SECONDARY TO CHRONIC RENAL FAILURE (CRF): EFFECTS OF rhGH THERAPY

Children with CRF are characterized by markedly short stature and Low bone mass. Thirteen prepobertal children with severe CRF(GFR<20.8 ml/min/1.73 m 2)and short stature (HSDS<3.6 below the mean)with a mean choronological age 6.7 ± 3.5yr. were studied using Dual X-ray Absorpsiometry before and after 6 months of treatment with rhGH (1 I.U. /Kg/Week) bone mass was measured in total body, lumbar spine (trabecular bone) and femoral neek (cortical bone). Total BMC was significantly lower in our patients compared to age matched healthy controls (443.2 ± 155.2 vs, 903.1 ± 369 g; p<0.003). After 6 months of rhGH treatment total BMC increased to 516.7 ± 147 g; p<0.05, in the group of CRF patients. Trabecular BMC increased from 0.496 ± 0.04 to 0.585 ± 0.1g/cm2 and cortical BMC increased from 0.605 ± 0.1 to 0.651 ± 0.08g/cm2 after 6 months of rhGH. Our findings indicate that children with CRF present with a low bone mass, and short term treatment with rhGH seems to increase their bone mineral content. Long term studies will be necessery to asses the real effect exerted by rhGH therapy on the skeleton of children with CRF as they increase their growth velocity.

Clinical evaluation of age-related changes of bone mineral content of cortical and trabecular bones by dual energy QCT

The potential capability of a new dual energy (DE) quantitative computed tomography (QCT) method, 4-equation 4-unknown method (DEQCT4E-4U), was evaluated for estimation of bone mineral density (BMD) as well as bone mineral content/cm width (BMC) in trabecular bone of lumbar vertebrae. Cortical BMD and BMC were also estimated by the single energy QCT method (SEQCT 80 kVp) and the age-related change of cortical BMD and the cortical BMC/trabecular BMC ratio was also studied. The result indicated that the estimation of the BMD combining analysis of BMC in trabecular bone obtained by the present method provides further knowledge concerning vertebral trabecular bone mineral status. The profiles of the age-related changes of the cortical BMD and cortical BMC/trabecular BMC ratio in females were markedly different from those in males. These results indicated that our method combining analysis of BMC (BMD) of cortical bone and trabecular bone was also found to provide valuable information to evaluate the vertebral bone mineral status.

Genetic determinants of bone mineral content at the spine and radius: A twin study

The possible role of genetic and/or environmental factors in determining bone mass has been investigated in 30 pairs of twins (16 monozygotic and 14 dizygotic) divided in two age groups (below and above 25 years of age). Bone mineral content was evaluated by single- and dual photon absorptiometry at the distol third of the radius for peripheral cortical bone and in the lumbar spine for the axial bone. The “within pair” variance has been used as an index of genetic influence. A significant ( p < 0.01) genetic determinant was found for the bone mass of the radius in adults and for the spinal bone mass in the age group younger than 25 years. The heritability index h 2 was 0.75 for cortical BMC and 0.88 for axial BMC. Such a genetic determinant could not conclusively be demonstrated in adult twins for the spine and in youngsters for the cortical bone, suggesting that environmental factors may play a more dominant role in growth of cortical bone during adolescence and diminution of axial bone during adult life.