Wrist Joint Skeletal Changes in Children With Transfusion-dependent Thalassemia.

BACKGROUND: Arthropathies and bone deformities are well known to occur in patients with thalassemia major and have been attributed to the disease or to its therapy. Before the advent of chelation therapy, these children developed widened diploic space and "hair-on-end" pattern in skull, "cobweb" pattern in the pelvis, and the lack of the normal concave outline in the long bones because of extensive marrow proliferation. After the introduction of iron-chelation therapy, these patients were noted to develop metaphyseal abnormalities and vertebral changes resembling spondylo-metaphyseal dysplasia. Only one study has shown some association of deferiprone (chelating agent) use with distal ulnar changes in these children. Our study was done to describe the skeletal changes and deformities in wrist joints of children with transfusion-dependent thalassemia and correlate them with age, mean pretransfusion hemoglobin level, mean serum ferritin level, and type and duration of chelation therapy in these children. METHODS: A total of 60 children with transfusion-dependent thalassemia from the thalassemia daycare center were examined. These children were divided into 3 groups on the basis of their age (group A: 2 to 6 y, group B: 6 to 10 y, and group C: 10 to 14 y). Detailed history, including treatment history, number of blood transfusions received over the last 1 year, clinical examination, and radiologic assessment of both forearm with wrists were done. RESULTS: The clinical and radiologic differences in radial and ulnar lengths increased significantly with the increasing age of these patients, the ulna being short. There was some correlation between increasing negative ulnar variance and distal radial articular angle with deferiprone consumption. CONCLUSION: Chelation therapy, particularly with deferiprone, may cause distal ulnar growth arrest causing ulnar shortening and progressive radial bowing in these children. LEVEL OF EVIDENCE: Level IV-case series.

Prospective Study Evaluating Changes in Bone Quality in Premenopausal Women With Breast Cancer Undergoing Adjuvant Chemotherapy.

BACKGROUND: Ovarian suppression from chemotherapy results in bone loss in premenopausal women with breast cancer (BC). Less is known about bone microarchitecture changes. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure volumetric bone density and trabecular and cortical microarchitecture in this population. MATERIALS AND METHODS: The primary endpoint was to assess changes in cortical thickness and trabecular bone density by HR-pQCT. Premenopausal women with stage I to III BC undergoing adjuvant chemotherapy underwent a bone mineral density (BMD) dual energy x-ray absorptiometry scan and HR-pQCT (voxel size, 82 microns) at baseline and 12 months. Paired t tests were used to observe the change over time in bone microarchitecture and areal and volumetric density. RESULTS: Eighteen patients were evaluated, of which 12 patients had baseline and matched 12-month imaging. The mean age was 45.2 years (range, 35-51 years), 17 (94%) patients had hormone receptor-positive BC, and 16 (89%) initiated tamoxifen. At 12 months, there was a significant decrease in femoral neck (P < .05) and lumbar spine and total hip (P < .01) BMD. Changes detected by HR-pQCT at 12 months included significant decreases in cortical thickness and area at the tibia (P < .05), and total and cortical volumetric BMD at the radius and tibia (P < .01), as well as an increase in tibial trabecular area (P < .05). CONCLUSION: Premenopausal women undergoing chemotherapy experience BMD decline and trabecular and cortical bone microarchitecture deterioration. In this population, future efforts should focus on therapy-induced bone loss and optimizing bone density-related management.

Fluoride intake and cortical and trabecular bone characteristics in adolescents at age 17: A prospective cohort study.

OBJECTIVE: To investigate the associations between period-specific and cumulative fluoride (F) intakes from birth to age 17 years, and radial and tibial bone measures obtained using peripheral quantitative computed tomography (pQCT). METHODS: Participants (n = 380) were recruited from hospitals at birth and continued their participation in the ongoing Iowa Fluoride Study/Iowa Bone Development Study until age 17. Fluoride intakes from water, other beverages, selected foods, dietary fluoride supplements and dentifrice were determined every 1.5-6 months using detailed questionnaires. Associations between F intake and bone measures (cortical and trabecular bone mineral content [BMC], density and strength) were determined in bivariate and multivariable analyses adjusted for height, weight, maturity offset, physical activity, and daily calcium and protein intake using robust regression analysis. RESULTS: Fluoride intake ranged from 0.7 to 0.8 mg F/d for females and from 0.7 to 0.9 mg F/d for males. Spearman correlations between daily F intake and pQCT bone measures were weak. For females, Spearman correlations ranged from r = -.08 to .21, and for males, they ranged from r = -.03 to .30. In sex-specific, height-, weight- and maturity offset- partially adjusted regression analyses, associations between females' fluoride intake and bone characteristics were almost all negative; associations for males were mostly positive. In the fully adjusted models, which also included physical activity, and protein and calcium intakes, no significant associations were detected for females; significant positive associations were detected between F intake from 14 to 17 years and tibial cortical bone content (ß = 21.40, P < .01) and torsion strength (ß = 175.06, P < .01) for males. CONCLUSION: In this cohort of 17-year-old adolescents, mostly living in optimally fluoridated areas, lifelong F intake from combined sources was weakly associated with bone pQCT measures.

Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

INTRODUCTION/PURPOSE: Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. METHODS: Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. RESULTS: Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). CONCLUSIONS: Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

The relationship between serum 25(OH)D and bone density and microarchitecture as measured by HR-pQCT.

UNLABELLED: The relation between serum 25-hydroxy vitamin D [25(OH)D] and bone quality is not well understood, particularly for high levels. We measured bone microarchitecture in three groups of people stratified by their serum 25(OH)D. There was a weak association of serum 25(OH)D and microarchitecture for this cross-sectional population, suggesting possible benefits to bone quality. INTRODUCTION: Vitamin D plays an important role in bone and mineral metabolism, but the relation between serum 25(OH)D and bone quality is not well understood. Here, we present a cross-sectional study that investigated a convenience group of participants from an ongoing health initiative in Alberta, Canada, who have been receiving daily vitamin D supplementation. METHODS: A total of 105 participants were organized into three groups based on their serum 25(OH)D levels: low (<75 nmol/L), medium (75-175 nmol/L), and high (>175 nmol/L). They were also assessed with 25(OH)D as a continuous variable. Average daily supplementation was 7670 ± 438 IU, and the change in 25(OH)D ranged from 22 to 33 % during the period of receiving supplements. We used high-resolution peripheral quantitative computed tomography measurements at the radius and tibia to assess bone microarchitecture. RESULTS: Microarchitectural parameters were not strongly associated with serum 25(OH)D. In the tibia, there were fewer trabeculae (TbN; p = 0.015) and a non-significant trend toward thicker trabeculae (p = 0.067) of the high group. Body mass index (BMI) was negatively associated with serum 25(OH)D levels (p < 0.001) and PTH levels (p < 0.001). There was no clinically significant relationship detected between high serum 25(OH)D and high serum calcium. CONCLUSION: These data suggest a weak relationship between serum 25(OH)D and bone microarchitecture in this population of mostly vitamin-D-sufficient participants, and there were no indications of negative effects related to the high supplementation levels. These data provided a basis to design and implement our 3-year dose-dependent randomized controlled trial investigating the effects of vitamin D supplementation on bone health outcomes.

The effect of combined calcium and cholecalciferol supplementation on bone mineral density in elderly women with moderate chronic kidney disease.

AIMS: To examine the effect of combined calcium and vitamin D3 supplementation on bone mineral density (BMD) inpatients with chronic kidney disease (CKD). METHODS: We performed a post-hoc analysis of the DECALYOS II, a 2-year randomized, double-blind, placebo-controlled study of 610 women randomized to: calcium-vitamin D3 fixed combination, calcium plus vitamin D3 separate combination, or placebo. Both active treatment groups received the same daily amount of calcium (1,200 mg) and vitamin D3 (800 IU). BMD of the distal radius was measured by single X-ray absorptiometry at baseline, 12 and 24 months. RESULTS: At baseline 47.2%, 36.4% and 16.4% of the study population had an eGFR ≥ 60, 45 -59, and < 45 ml/min/1.73 m2, respectively. Both active regimens vs. placebo markedly increased serum 25-hydroxyvitamin D levels from baseline in all eGFR groups (p 0.22 for all time points). CONCLUSION: Combined calcium and vitamin D3 supplementation was effective in reducing rate of BMD loss in women with moderate CKD.

Prevention of nutritional rickets in Nigerian children with dietary calcium supplementation.

Nutritional rickets in Nigerian children usually results from dietary calcium insufficiency. Typical dietary calcium intakes in African children are about 200mg daily (approximately 20-28% of US RDAs for age). We sought to determine if rickets could be prevented with supplemental calcium or with an indigenous food rich in calcium. We enrolled Nigerian children aged 12 to 18months from three urban communities. Two communities were assigned calcium, either as calcium carbonate (400mg) or ground fish (529±109mg) daily, while children in all three communities received vitamin A (2500IU) daily as placebo. Serum markers of mineral homeostasis and forearm bone density (pDEXA) were measured and radiographs were obtained at enrollment and after 18months of supplementation. The overall prevalence of radiographic rickets at baseline was 1.2% and of vitamin D deficiency [serum 25(OH)D<12ng/ml] 5.4%. Of 647 children enrolled, 390 completed the 18-month follow-up. Rickets developed in 1, 1, and 2 children assigned to the calcium tablet, ground fish, and control groups, respectively (approximate incidence 6.4/1000 children/year between 1 and 3years of age). Children who developed rickets in the calcium-supplemented groups had less than 50% adherence. Compared with the group that received no calcium supplementation, the groups that received calcium had a greater increase in areal bone density of the distal and proximal 1/3 radius and ulna over time (P<0.04). We conclude that calcium supplementation increased areal bone density at the radius and ulna, but a larger sample size would be required to determine its effect on the incidence of rickets.

Cortical and trabecular bone at the radius and tibia in postmenopausal breast cancer patients: a Peripheral Quantitative Computed Tomography (pQCT) study.

Bone morbidity associated with antineoplastic treatment is a significant health concern for postmenopausal breast cancer patients. Trials have demonstrated that adjuvant therapy with an Aromatase Inhibitor is associated with an increase in musculoskeletal disorders and bone fractures. The objective of this study was to utilize Peripheral Quantitative Computed Tomography (pQCT) to assess in vivo trabecular and cortical volumetric bone at peripheral skeletal sites in healthy postmenopausal women and breast cancer patients prescribed Anastrozole. Fifty-eight women were recruited for this study: 27 breast cancer patients and 31 healthy control participants. pQCT measurements were taken at distal and diaphyseal sites of the radius and tibia using a Stratec XCT-2000 pQCT scanner. Bone measurement values for total density and total content at the 4% radius; total and cortical content as well as cortical density at the 20% radius; total density at the 4% tibia; and cortical density at the 38% tibia were found to be significantly lower in breast cancer patients. Moreover, the duration of time on Anastrozole showed a significant negative correlation with the following measurements: total content at the 4% radius (r=-0.36, p<0.01); total content (r=-0.33, p<0.05), cortical content (r=-0.34, p<0.05) and cortical density (r=-0.44, p<0.01) at the 20% radius; as well as cortical density (r=-0.39, p<0.01) and cortical content (r=-0.27, p<0.05) at the 38% tibia. Overall, the breast cancer patients demonstrated significantly lower values for volumetric bone density and content at the radius and tibia compared with healthy postmenopausal women. Furthermore, this novel study found adverse effects from Anastrozole treatment primarily in cortical bone.

The use of a synthetic oxygen carrier-enriched hydrogel to enhance mesenchymal stem cell-based bone formation in vivo.

A major hurdle to surmount in bone-tissue engineering is ensuring a sufficient oxygen supply to newly forming tissue to avoid cell death or delayed development of osteogenic features. We hypothesized that an oxygen-enriched hydrogel scaffold would enhance tissue-engineered bone formation in vivo. To test this, we used a well-characterized mesenchymal stem cell (MSC) line, Tet-off BMP2 MSC, whose cells were engineered to express recombinant human bone morphogenetic protein-2. Cells were suspended in hydrogel supplemented with perfluorotributylamine (PFTBA) and implanted subcutaneously in an ectopic site, a radial bone defect, or a lumbar paravertebral muscle (mouse model of spinal fusion) in C3H/HeN mice. For controls, we used cells suspended in the same gel without PFTBA. In the ectopic site, there were significant increases in bone formation (2.5-fold increase), cell survival, and osteocalcin activity in the PFTBA-supplemented groups. PFTBA supplementation significantly increased structural parameters of bone in radial bone defects and triggered a significant 1.4-fold increase in bone volume in the spinal fusion model. We conclude that synthetic oxygen carrier supplementation of tissue-engineered implants enhances ectopic bone formation and yields better bone quality and volume in bone-repair and spinal fusion models, probably due to increased cell survival.

Wintertime vitamin D supplementation inhibits seasonal variation of calcitropic hormones and maintains bone turnover in healthy men.

Vitamin D is suggested to have a role in the coupling of bone resorption and formation. Compared with women, men are believed to have more stable bone remodeling, and thus, are considered less susceptible to the seasonal variation of calcitropic hormones. We examined whether seasonal variation exists in calcitropic hormones, bone remodeling markers, and BMD in healthy men. Furthermore, we determined which vitamin D intake is required to prevent this variation. Subjects (N = 48) were healthy white men 21-49 yr of age from the Helsinki area with a mean habitual dietary intake of vitamin D of 6.6 +/- 5.1 (SD) microg/d. This was a 6-mo double-blinded vitamin D intervention study, in which subjects were allocated to three groups of 20 microg (800 IU), 10 microg (400 IU), or placebo. Fasting blood samplings were collected six times for analyses of serum (S-)25(OH)D, iPTH, bone-specific alkaline phosphatase (BALP), and TRACP. Radial volumetric BMD (vBMD) was measured at the beginning and end of the study with pQCT. Wintertime variation was noted in S-25(OH)D, S-PTH, and S-TRACP (p < 0.001, p = 0.012, and p < 0.05, respectively) but not in S-BALP or vBMD in the placebo group. Supplementation inhibited the winter elevation of PTH (p = 0.035), decreased the S-BALP concentration (p < 0.05), but benefited cortical BMD (p = 0.09) only slightly. Healthy men are exposed to wintertime decrease in vitamin D status that impacts PTH concentration. Vitamin D supplementation improved vitamin D status and inhibited the winter elevation of PTH and also decreased BALP concentration. The ratio of TRACP to BALP shows the coupling of bone remodeling in a robust way. A stable ratio was observed among those retaining a stable PTH throughout the study. A daily intake of vitamin D in the range of 17.5-20 microg (700-800 IU) seems to be required to prevent winter seasonal increases in PTH and maintain stable bone turnover in young, healthy white men.

Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

UNLABELLED: Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. INTRODUCTION: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age. MATERIALS AND METHODS: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. RESULTS: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). CONCLUSIONS: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.

In vivo application of 3D-line skeleton graph analysis (LSGA) technique with high-resolution magnetic resonance imaging of trabecular bone structure.

Over the last several years magnetic resonance (MR) imaging has emerged as a means of measuring in vivo 3D trabecular bone structure. In particular, MR based diagnosis could be used to complement standard bone mineral density (BMD) methods for assessing osteoporosis and evaluating longitudinal changes. The aim of this study was to demonstrate the feasibility of using the 3D-LSGA technique for the evaluation of trabecular bone structure of high-resolution MR images, particularly for assessing longitudinal changes, in vivo. First, the reproducibility of topological 3D-LSGA based measurements was evaluated in a set of seven volunteers, and coefficients of variations ranged from 3.5% to 6%. Second, high-resolution MR images of the radius in 30 postmenopausal women from a placebo controlled drug study (Idoxifene), divided into placebo ( n=9) and treated ( n=21) groups, were obtained at baseline (BL) and after 1 year of treatment (follow-up, FU). In addition, dual X-ray absorptiometry (DXA) measures of BMD were obtained in the distal radius. Standard morphological measurements based on the mean intercept length (MIL) technique as well as 3D-LSGA based measurements were applied to the 3D MR images. Significant changes from BL to FU were detected, in the treated group, using the topological 3D-LSGA based measurements, morphological measures of volume of connected trabeculae and App Tb.N from MIL analysis. The duration of the study was short, and the number of patients remaining in the study was small, hence these results cannot be interpreted with regard to a true therapeutic response. Furthermore, the site (wrist) and the drug (idoxifene) are not optimal for follow-up study. However, this paper demonstrated the feasibility of using 3D-LSGA based evaluation coupled with in vivo high-resolution MR imaging as a complementary approach for the monitoring of trabecular bone changes in individual subjects.

Vertebral fracture and cortical bone changes in corticosteroid-induced osteoporosis.

Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21-18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors ( p<0.0001) in the control group. In the steroid group, however, the cortical bone mineral density (BMD) ( p = 0.001), RCV ( p<0.0001) and SSI ( p = 0.001) were found to be significant predictors, but not trabecular BMD ( p = 0.176). For comparison between the two groups, thresholds of all parameters for vertebral fracture were also calculated by the point of coincidence of sensitivity with specificity in ROC testing and the 90th percentile value. Although a rise in fracture threshold in the steroid group was suggested, considerable difference in the values obtained by the two methods of calculation precluded any conclusion. High-dose oral steroid administration was associated with an increased risk of fracture. Cortical bone parameters obtained by pQCT could play a role as good predictors of future corticosteroid-induced vertebral fractures.

Changes in spine and radius bone density during long-term hormone replacement.

Lumbar spine and mid-radius bone mineral density was measured repeatedly in 48 postmenopausal women who completed 7 years of taking either a 500 mg x day(-1) calcium supplement (n = 22) or calcium supplementation with hormone replacement therapy. The hormone replacement was either a low dose (n = 15) or a moderate dose (n = regime. The purpose of the measurements was to establish the long-term pattern of change in bone mineral mass produced by continued hormone replacement. The calcium-only group lost bone mineral mass at the radius, while the spine, bone was preserved. Low dose hormone replacement preserved radius bone. Moderate dose replacement increased bone mineral mass at the spine and preserved radius bone.

Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.

Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary cross-linked collagen at 6 months correlated with long-term bone density changes at the hip (r = -0.35, p < 0.01), trochanter (r = -0.36, p < 0.01), PA spine (r = -0.41, p < 0.01), and total body (r = -0.34, p < 0.05). At 6 months, patients with the greatest drop in urinary cross-linked collagen (65% or more) demonstrated the greatest gains in total hip, trochanteric, and vertebral bone density (all p < 0.05). A 30% decrease in urinary cross-linked collagen at 6 months predicted a bone density increase of 2.8-4.1% for the hip regions and 5.8-6.9% for the spine views at the 2.5-year time point (p < 0.05). There were no substantive associations between changes in biochemical markers and bone density in the placebo group. Alendronate therapy was associated with significant long-term gains in BMD at all clinically relevant sites, including the hip, in elderly women. Moreover, these improvements were associated with early decreases in biochemical markers of bone turnover. Early dynamic decreases in urinary cross-linked collagen can be used to monitor and predict long-term response to bisphosphonate therapy in elderly women. Future studies are needed to determine if early assessment improves long-term patient compliance or uncovers poor compliance, thereby aiding the physician in maximizing the benefits of therapy.

Long term effects of boron on layer bone strength and production parameters.

1. The effects of dietary boron (0, 50, 100, 200, and 400 mg/kg) on bone strength characteristics and egg production of white leghorn layers were investigated. 2. The shear fracture energy increased in the tibia and radius at 72 weeks for birds started on the 200 mg/kg supplement at 32 weeks of age. 3. The shear force, stress, and fracture energy of the tibia and radius increased for the non-egg producing birds at 72 weeks. 4. Bird body weight, food consumption, egg weight, and egg production all decreased at 400 mg/kg boron. 5. Boron concentrations in the breast, liver, thigh and bone tissue increased with increasing concentrations of supplemental boron.

The effect of calcium supplementation on bone density during lactation and after weaning.

BACKGROUND: Women may lose bone during lactation because of calcium lost in breast milk. We studied whether calcium supplementation prevents bone loss during lactation or augments bone gain after weaning. METHODS: We conducted two randomized, placebo-controlled trials of calcium supplementation (1 g per day) in postpartum women. In one trial (the study of lactation), 97 lactating and 99 nonlactating women were enrolled a mean (+/-SD) of 16+/-2 days post partum. In the second trial (the study of weaning), 95 lactating women who weaned their infants in the 2 months after enrollment and 92 nonlactating women were enrolled 5.6+/-0.8 months post partum. The bone density of the total body, lumbar spine, and forearm was measured at enrollment and after three and six months. RESULTS: The bone density of the lumbar spine decreased by 4.2 percent in the lactating women receiving calcium and by 4.9 percent in those receiving placebo and increased by 2.2 and 0.4 percent, respectively, in the nonlactating women (P<0.001 for the effect of lactation; P= 0.01 for the effect of calcium). After weaning, the bone density of the lumbar spine increased by 5.9 percent in the lactating women receiving calcium and by 4.4 percent in those receiving placebo; it increased by 2.5 and 1.6 percent, respectively, in the nonlactating women (P<0.001 for the effects of lactation and calcium). There was no effect of either lactation or calcium supplementation on bone density in the forearm, and there was no effect of calcium supplementation on the calcium concentration in breast milk. CONCLUSIONS: Calcium supplementation does not prevent bone loss during lactation and only slightly enhances the gain in bone density after weaning.

Complementary medical treatment for Colles' fracture: a comparative, randomized, longitudinal study.

In 45 women with Colles' fracture, two types of complementary medical treatment (calcitonin with calcium [SCT+Ca] and calcium alone [Ca]) were compared with placebo. Consecutive patients were assigned randomly to one of the three study groups at the time of inclusion in the study: 15 women (68.6 +/- 5.7 years) were given 100 IU/day I.M. of SCT plus 1200 mg of elemental Ca for 10 successive days each month; 15 women (71.7 +/- 6.1 years) were given only 1200 mg of elemental Ca for 10 days each month; and 15 women (66.9 +/- 7. 9 years) were treated with placebo. Biochemical and radiogrammetric studies were made at baseline and after 1 year of treatment. In the SCT+Ca group tartrate-resistant acid phosphatase decreased (Wilcoxon test, P = 0.014) and the metacarpal index and the cortical and total area (CA/TA) ratio increased (both P = 0.001). In the group treated with Ca alone, no changes were observed. In the placebo group, the metacarpal index and CA/TA decreased (P = 0.015 and P = 0.007, respectively). Ca alone, at the dosage used here, inhibited bone loss after Colles' fracture. The addition of SCT to Ca administration not only impeded bone loss but significantly increased cortical bone mass.

Effect of a calcium and phosphorus-enriched formula on bone mineralization and bone growth in preterm infants after discharge from hospital.

At discharge from hospital, 36 preterm infants (birthweight < 1,800 g) were randomized to be given either a standard formula or an identical formula enriched with calcium (47 vs. 80 mg/100 ml) and phosphorus (30 vs. 45 mg/100 ml) exclusively until they reached a corrected age of 3 months, thereafter beikost and other formulas were introduced into the diet. Weight, head circumference and radial and body length were measured and radial bone mineral content (BMC) and bone width (BW) determined by single photon absorptiometry at discharge, at 3 and at 6 months of corrected age. Additionally, an X-ray of the wrist was taken and serum alkaline phosphatase activity determined at discharge, and the latter repeated at 3 months. Bone mineral content, bone width, and the individual increments of both parameters were significantly higher in infants fed the enriched formula at 3 months of age, but these differences were less pronounced at 6 months.