Decrease In Bone Mineral Content Research Articles

Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass.

Little is known about the effects on the skeleton of laparoscopic Roux-en-Y gastric bypass (LRGB) surgery for morbid obesity and subsequent weight loss. We compared 25 patients who had undergone LRGB 11 +/- 3 months previously with 30 obese controls matched for age, gender, and menopausal status. Compared with obese controls, patients post LRGB had significantly lower weight (92 +/- 16 vs. 133 +/- 20 kg; P < 0.001) and body mass index (31 +/- 5 vs. 48 +/- 7 kg/m(2); P < 0.001). Markers of bone turnover were significantly elevated in patients post LRGB compared with controls (urinary N-telopeptide cross-linked collagen type 1, 93 +/- 38 vs. 24 +/- 11 nmol bone collagen equivalents per mmol creatinine; and osteocalcin, 11.6 +/- 3.4 vs. 7.6 +/- 3.6 ng/ml; both P < 0.001). Fifteen patients were studied prospectively for an average of 9 months after LRGB. They lost 37 +/- 9 kg and had a 29 +/- 8% fall in body mass index (both P < 0.001). Urinary N-telopeptide cross-linked collagen type 1 increased by 174 +/- 168% at 3 months (P < 0.01) and 319 +/- 187% at 9 months (P < 0.01). Bone mineral density decreased significantly at the total hip (7.8 +/- 4.8%; P < 0.001), trochanter (9.3 +/- 5.7%; P < 0.001), and total body (1.6 +/- 2.0%; P < 0.05), with significant decreases in bone mineral content at these sites. In summary, within 3 to 9 months after LRGB, morbidly obese patients have an increase in bone resorption associated with a decrease in bone mass. Additional studies are needed to examine these findings over the longer term.

Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy

HE ABNORMALITIES of the skeleton in chronic kidney disease (CKD), collectively known as renal osteodystrophy, are an important cause of morbidity and decreased quality of life. In the management of patients with kidney disease, it is necessary to have a rational approach to the diagnosis and assessment of renal osteodystrophy in order to devise a treatment plan that hopefully will lead to an improved outcome. In the past, the term renal osteodystrophy was mainly equated only with abnormalities of bone turnover, but as described in the article by Cunningham and Sprague 1 in this same issue, renal osteodystrophy is a complex disorder of compromised bone strength in CKD patients. While osteoporosis is a term used to describe fragile bones prone to fracture in the general population and is most often assessed by dual x-ray absorptiometry (DEXA), renal osteodystrophy should be the principal term to describe fragile bones prone to fracture and other morbidities in CKD. Renal osteodystrophy is a function of bone turnover (assessed by bone biopsy), bone density (assessed by DEXA or quantitative CT [qCT]), and bone architecture, but the principal determinant of bone fragility in CKD is abnormal bone turnover. However, diagnosing and treating bone turnover abnormalities remains challenging. Our discussion group met to assess the current state of knowledge, understand the basis of our current therapy, and identify the information that needs to be gathered to improve the therapy of bone turnover and thereby improve the disorder of renal osteodystrophy. A number of important questions, listed in Table 1, were considered.

Effect of JTC-801 (nociceptin antagonist) on neuropathic pain in a rat model

JTC-801, a nociceptin antagonist, may alleviate neuropathic pain because nociceptin has been shown to produce pain modulation. We report that JTC-801 alleviates heat-evoked hyperalgesia and investigated the possible protective effect on osteoporosis induced by chronic constriction injury (CCI) in rats. JTC-801 was given orally to rats with CCI at 0% (vehicle), 0.03% (low dose), or 0.06% (high dose) in food. Paw withdrawal latency (PWL) to heat, bone mineral content (BMC) and bone mineral density (BMD) of the whole tibial bone were measured. JTC-801 dose-dependently normalized PWL. Although JTC-801 did not inhibit a CCI-induced decrease in BMC and BMD, it inhibited an increase in the number of osteoclasts in the JTC-801 groups. JTC-801, given orally in food, alleviated heat-evoked hyperalgesia in CCI rats, suggesting that it is useful for the treatment of neuropathic pain.

Hypocalcemia and osteopathy in mice with kidney-specific megalin gene defect.

Megalin is an endocytic receptor highly expressed in the proximal tubules of the kidney. Recently, we demonstrated that this receptor is essential for the renal uptake and conversion of 25-OH vitamin D3 to 1,25-(OH)2 vitamin D3, a central step in vitamin D and bone metabolism. Unfortunately, the perinatal lethality of the conventional megalin knockout mouse model precluded the detailed analysis of the significance of megalin for calcium homeostasis and bone turnover in vivo. Here, we have generated a new mouse model with conditional inactivation of the megalin gene in the kidney by using Cre recombinase. Animals with a renal-specific receptor gene defect were viable and fertile. However, lack of receptor expression in the kidney results in plasma vitamin D deficiency, in hypocalcemia and in severe bone disease, characterized by a decrease in bone mineral content, an increase in osteoid surfaces, and a lack of mineralizing activity. These features are consistent with osteomalacia (softening of the bones) as a consequence of hypovitaminosis D and demonstrate the crucial importance of the megalin pathway for systemic calcium homeostasis and bone metabolism.

What we have learned about long-term cementless fixation from autopsy retrievals.

The current authors summarize insights gained from their experience studying uncemented porous-coated femoral and acetabular hip replacement components retrieved at autopsy. For femoral components, autopsy studies showed that osseointegration occurs over an average 35% of the porous surface with the most predictable ingrowth occurring near the termination of the porous coating. The bone ingrowth pattern causes a predictable bone remodeling pattern: an overall decrease in bone mineral content (mean, 23% loss) occurring on a gradient with the most loss proximally and the least distally. This pattern occurs regardless of the implant's level of coating, mirrors the gradient of strain reduction, and because it is recognized easily, can be used by orthopaedists to distinguish between components with and without bone ingrowth on standard radiographs. Studies also have shown that femoral bone loss is more related to the characteristics of the implanted femur than any other variable. On the acetabular side, bone ingrowth is more unpredictable and occurs randomly. Although the amount of acetabular bone ingrowth averaged 32%, it ranged from 3% to 84%. Unfortunately, a consistent pelvic remodeling pattern has not been associated with an implanted porous-coated uncemented cup. Consequently, orthopaedists cannot determine radiographically whether an acetabular component truly is bone ingrown. Overall, autopsy studies have contributed to a basic understanding of the histologic and radiographic appearance of osteointegrated porous-coated implants and have confirmed the durability of this three-dimensional fixation even in the presence of osteolysis.

Role of fos and src in Cadmium-Induced Decreases in Bone Mineral Content in Mice

Cadmium decreases bone mineral in mice and stimulates osteoclast formation and activity in cell culture. Bones from fos-deficient mice contain very few osteoclasts; src−/− bones contain osteoclasts that fail to activate. Fos−/− and src−/− mice develop osteopetrotic bones and their teeth do not erupt. These mice were used to determine if cadmium requires c-Fos or c-Src and secondarily functional osteoclasts to decrease bone mineral content. Mice heterozygous for fos deficiency were mated to produce fos−/− and fos+/o (wild-type) offspring. Pups were divided into four groups: fos+/o, Cd−; fos+/o, Cd+; fos−/−, Cd−; and fos−/−, Cd+. Cd+ pups received daily sc injections (50 μg Cd/kg) on days 17–20 and Cd in drinking water thereafter (10 ppm, days 21–27; 20 ppm, days 27–50). An analogous protocol was followed mating mice heterozygous for src deficiency. For acute exposures, 50-day-old mice were placed on a low-calcium diet and given two sequential 100 μg Cd doses by gavage, and feces were monitored for excretion of bone calcium. Continuous exposure results demonstrate that cadmium (1) significantly decreased bone calcium content (14–15%) and concentration (12–13%) in both fos+/o and fos−/− mice, (2) doubled multinucleated osteoclast-like cell number in fos−/− bones, and (3) stimulated tooth eruption in 40% of fos−/− mice. Cd gavage stimulated bone calcium excretion in both fos+/o and fos−/− mice. In contrast, cadmium had no effect on bones or teeth in src−/− mice. Results indicate that cadmium can decrease bone mineral via a c-Fos-independent pathway; however, c- Src is required for cadmium to stimulate bone remodeling and tooth eruption pathways.

Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo.

FGF-23 is involved in the pathogenesis of two similar hypophosphatemic diseases, autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and tumor-induced osteomalacia (TIO). We have shown that the overproduction of FGF-23 by tumors causes TIO. In contrast, ADHR derives from missense mutations in FGF-23 gene. However, it has been unclear how those mutations affect phosphate metabolism. Therefore, we produced mutant as well as wild-type FGF-23 proteins and examined their biological activity. Western blot analysis using site-specific antibodies showed that wild-type FGF-23 secreted into conditioned media was partially cleaved between Arg(179) and Ser(180). In addition, further processing of the cleaved N-terminal portion was observed. In constrast, mutant FGF-23 proteins found in ADHR were resistant to the cleavage. In order to clarify which molecule has the biological activity to induce hypophosphatemia, we separated full-length protein, the N-terminal and C-terminal fragments of wild-type FGF-23. When the activity of each fraction was examined in vivo, only the full-length FGF-23 decreased serum phosphate. Mutant FGF-23 protein that was resistant to the cleavage also retained the activity to induce hypophosphatemia. The extent of hypophosphatemia induced by the single administration of either wild-type or the mutant full-length FGF-23 protein was similar. In addition, implantation of CHO cells expressing the mutant FGF-23 protein caused hypophosphatemia and the decrease of bone mineral content. We conclude that ADHR is caused by hypophosphatemic action of mutant full-length FGF-23 proteins that are resistant to the cleavage between Arg(179) and Ser(180).

MUSCLE MASS, BONE MINERAL CONTENT AND FAT MASS IN HEMIPLEGIC STROKE PATIENTS

PURPOSE: The aim of this study was to investigate body composition changes that occur due to immobilization on the affected side in hemiplegic stroke patients. Patients with hemiplegia experience decreases in muscle mass, bone demineralization and increases in fat mass. METHODS: 23 hospitalized elderly men with a mean age 72.1 ± 8.2 years. All the patients were post stroke with hemiparesis or muscle weakness on one side. Muscle mass, bone mineral content (BMC) and fat mass were assessed with Dual X-ray Absorptiometry (DEXA) Lunar DPX-L model for both affected and unaffected side. RESULTS: A t-test was used to examine significant differences between the affected and unaffected sides. The affected side had 5% (p = .001) higher fat mass than the unaffected side. No difference was found between the sides in muscle mass and BMC (p = .920; p = .122 respectively). However, the affected side showed a 4.5% decrease in BMC compared to the unaffected side. CONCLUSIONS: The study failed to show significant difference between affected and unaffected sides in muscle mass and BMC. However there is a trend of lower BMC in the affected side. The lack of statistical significance in muscle and bone mass between the two sides might be attributed to the fact that these patients were very deconditioned at the time of the study and that loss of muscle and bone mass was generalized throughout the body because of extended periods of inactivity. If activity is reinitiated, lean muscle mass may be regained; in contrast, extended inactivity generalizes deficits found in these compartments. However, loss of BMC and fat accumulation appears difficult to prevent, regardless of lean muscle mass effect. FUNDING ACKNOWLEDGEMENTS: Funded by National VA merit #2117, Retirement Research Foundation; the NIH National Center for Research Resources GCRC Grant #MO1 RR02719; the NIH NIA Gerontology Research Center; John Hopkins University School of Medicine Institutional Research Grants; the Houston VAMC Center for Healthy Aging with Disabilities; the Cheasapeake Physicians' Professional Association Research and Education Fund; and the Levindale Care for the Aged Research Fund.

Body composition changes in protease inhibitor-naive HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors.

In the era of highly active antiretroviral treatment (HAART), there are insufficient data regarding lipodystrophy syndromes in HIV-1-infected patients treated with regimens that do not include protease inhibitors (PIs). We studied changes in body composition in HIV-1-infected patients before and 2 years after starting a non-PI-containing antiretroviral treatment regimen. We studied retrospectively the whole body dual energy X-ray absorptiometry (DEXA) scans of 23 PI-naive HIV-1-infected patients (17 males, six females), aged 37.4 +/- 9.3 years with mean CD4 count 401 +/- 130 cells/microL. Thirteen patients were on zidovudine (ZDV) + lamivudine (3TC) and 10 on ZDV + didanosine (ddI). Subjects were evaluated before the beginning of antiretroviral treatment and approximately 24 months later. For each patient body weight, CD4 T-cell counts, bone mineral content (BMC), bone mineral density (BMD) and whole body as well as regional fat and lean body mass were evaluated. A significant decrease in BMC was observed, although the T scores remained within the normal limits. Our patients also exhibited a significant decrease in body weight due almost exclusively to fat loss, while lean mass was minimally affected. Fat loss was statistically significant in the arms and legs, but not in the trunk. The above changes were most prominent in the ZDV + 3TC treatment group; in this group of patients, fat loss was also evident in the trunk. Patients on ZDV + ddI, on the other hand, only showed a significant increase in their legs' lean mass; they preserved their total fat mass and exhibited no other significant changes between the two assessments. Dual NRTI therapy contributes to fat loss and reduction of bone mineral content in otherwise healthy, clinically stable, PI-naive HIV-infected adults. Compared with patients on ZDV + ddI, patients on ZDV + 3TC had a more prominent fat loss in all body regions.

Bone loss at the femoral neck in premenopausal white women: effects of weight change and sex-hormone levels.

To investigate whether bone loss occurs in the premenopause, we measured the bone mineral content (BMC), bone mineral density (BMD), and bone area in the spine (L2-L4), femoral neck, and total hip, as well as the sex hormone levels of 130 healthy premenopausal white women (age, 31-50 yr) at least three times over 1-9 yr. We found an increase in all three bone measurements at the spine but no change in volumetric density. Neither could we detect any age-related changes in any of the three measurements in the total hip. In contrast, we detected a significant decrease in femoral neck BMD over time, due to a decrease in BMC and increase in bone area. Greater loss in femoral neck BMD was associated independently with weight loss and lower levels of estrone sulfate or E2. Separating the women into those with FSH spikes (>20 IU/liter) and women with consistently low FSH, we found the latter group had smaller decrease in BMD and that the decrease was due less to a decline in BMC and more to an increase in bone area. In summary, femoral neck BMD decreases in premenopausal women, particularly those with lower levels of estrogens resulting from slowing ovarian function despite regular menses. This decrease can be offset by more rapid weight gain.

The evaluation of a rat model for the analysis of densitometric and biomechanical properties of tumor-induced osteolysis

Pathologic fractures from a reduction in bone mass and strength are a debilitating complication affecting the quality of life of individuals with metastatic lesions. There are a number of existing animal models for studying the effects of bone metastases experimentally, but these models are unsuitable for measuring structural changes in metastatic bone. Our goal was to present an in vivo model for directly investigating the densitometric and structural consequences of tumor-induced osteolysis in long bones. One femur from female Sprague Dawley rats was implanted with Walker Carcinosarcoma 256 malignant breast cancer cells or with a Sham implant. After 28 days, the animals were killed, and both femora of each animal evaluated using histomorphometry, densitometry, and mechanical testing. Compared to Sham-operated controls, we found an 11% decrease in bone mineral content, a 9% decrease in bone mineral density using dual energy X-ray absorptiometry, and a 16% decrease in bone density using peripheral quantitative computed tomography in the group with tumor cell implants. In addition, failure torque was decreased by 35% compared to the contralateral controls and by 41% compared to the Sham-operated controls. Torsional stiffness in the tumor cell-implanted femora was decreased by 35% compared to contralateral controls and by 39% compared to Sham-operated controls. Bone density was only weakly to moderately associated with bone strength in our model. By creating reproducible localized tumor-induced osteolytic lesions in a long bone, this model provides the most direct evaluation of the structural consequences of bone metastases. In the future, this model may provide a method for determining the effects of new therapeutic approaches on the preservation of bone mass and bone strength in the presence of metastatic bone disease.

Texture analysis of X-ray radiographs is a more reliable descriptor of bone loss than mineral content in a rat model of localized disuse induced by the Clostridium botulinum toxin

Botulism is a generalized paralyzing disease caused by the toxin of Clostridium botulinum (BTX). The toxin acts 3–4 days after injection by blocking the release of acetylcholine to the muscle. Six Wistar rats received a 2-U injection of BTX in the right quadriceps. Six rats were similarly injected with saline and were used as control. Paralysis of the quadriceps was obtained 4–5 days after the injection. Animals were killed 4 weeks after the BTX injection. The bone mineral content (BMC) was measured by dual-energy X-ray absorptiometry (DXA) on the femur and tibia. No side-to-side difference was observed for BMC on the whole tibia and femur in the BTX group. When subregions were selected in the bones, a significant decrease in BMC was obtained on the proximal tibia (−17.4 ± 2.5%, p < 0.02). No significant difference could be observed on the proximal or distal femur, nor on the diaphyseal shafts. Numeric X-rays were done and a region of interest was transferred to an image analyzer. The texture of the trabecular bone was analyzed by the run length and fractal methods (skyscrapers and blanket). Significant differences were obtained on the proximal tibia for all methods except with fractal skyscrapers. On the distal femur, significant differences were obtained with the run length method, and the skyscrapers and the blanket method in the vertical direction. No differences were obtained with any method on the tibia and femur from control animals. Bone is a highly anisotropic material and its architecture at the microscopic level is conditioned by strains. The trabecular pattern differs in the proximal tibia than in the distal femural. Depending on the trabecular anisotropy, the algorithms can be more or less pertinent. BTX induced a significant bone loss on the bony subparts that are directly influenced by disuse. Texture analysis of X-ray images can reveal differences that were not evidenced by naked eyes. However, a combination of several methods appears necessary to appreciate the bone loss.

Disproportional Skeletal Growth and Markedly Decreased Bone Mineral Content in Growth Hormone Receptor −/− Mice

Growth hormone (GH) is important for skeletal growth as well as for a normal bone metabolism in adults. The skeletal growth and adult bone metabolism was studied in mice with an inactivated growth hormone receptor (GHR) gene. The lengths of femur, tibia, and crown–rump were, as expected, decreased in GHR−/− mice. Unexpectedly, GHR−/− mice displayed disproportional skeletal growth reflected by decreased femur/crown–rump and femur/tibia ratios. GHR−/− mice demonstrated decreased width of the growth plates in the long bones and disturbed ossification of the proximal tibial epiphysis. Furthermore, the area bone mineral density (BMD) as well as the bone mineral content (BMC)/body weight were markedly decreased in GHR−/− mice. The decrease in BMC in GHR−/− mice was not due to decreased trabecular volumetric BMD but to a decreased cross-sectional cortical bone area In conclusion, GHR−/− mice demonstrate disproportional skeletal growth and markedly decreased bone mineral content.

Bone mass changes during pregnancy and lactation in the rat

We examined bone mass changes in the total, axial, and appendicular skeleton as well as in the different subareas of femur and tibia in rats fed on a normal calcium diet. A total of 16 virgin Wistar rats, approximately 5 months of age (270 ± 30 g), were assigned to two groups of eight rats each. One group was mated and, for each pregnant rat, a nonpregnant control rat was studied simultaneously. Weaning was performed when the pups reached 38 ± 3 g body weight. At the beginning (t = 0), on the first day postpartum (t = 22 days), and at weaning (t = 45 days), total skeleton bone mineral content (BMC), area, and bone mineral density (BMD) were determined by dual-energy X-ray absorptiometry (DXA) in vivo under anesthesia. Body weight increased significantly during pregnancy ( p < 0.05) and decreased at weaning, whereas control rats showed a slow, gradual increment without reaching a significant difference. During pregnancy, BMC and area of the total skeleton increased significantly in pregnant rats, but the changes in BMD were not different compared with the control group. A completely different pattern was observed between groups during the 23 days of lactation. While the skeleton continued to grow in the control group (BMC and area increased), the total skeleton of lactating rats showed no change in area (size), small decreases in BMC, and a significant decrease in BMD ( p < 0.05). Consequently, although BMC and BMD of both groups were similar at the time of delivery, BMC was 12.0% lower and BMD 4.9% lower at the end of lactation in the lactating rats compared with the control group. The contribution of the maternal skeleton to the lactation period was not similar; that is, the areas with the highest trabecular component showed the greater average differences in BMD at the time of weaning (proximal tibia −19.9%, distal femur −12.6%, spine −10.9%) ( p < 0.05), compared with relatively minor, nonsignificant losses in areas where cortical bone predominates (distal tibia −5%, middle tibia −5.2%). Our experimental results demonstrated the usefulness of DXA in vivo to visualize changes in BMD during the reproductive cycle of the rat. Moreover, the data confirm that normal pregnancy in the rat appears to exert little influence on bone, whereas lactation induces significant bone loss, mainly in the areas of predominant trabecular bone.

Long-term metabolic effects in patients with urinary diversion.

The use of intestinal segments in genitourinary reconstruction could influence vitamin metabolism and affect the skeletal bone and its mineral content in the long term. In 137 patients, serum levels of the vitamins A, B1, B2, B6, B12, D, and E and of folic acid, bile acid, and ammonia as well as levels of intracorpuscular vitamin B12 and folic acid were examined and a red blood cell count was performed. The patients were divided into three groups (< or = 2 years, > 2 to < or = 4 years, and > 4 years after surgery) as well as into children and adults. In addition, bone mineral density (dual-photon absorptiometry) was measured in 25 patients. Of these, 16 patients were approximately 16.8 years s/p rectal reservoir, 6 were approximately 20.5 years s/p colonic conduit, two were 6 and 8 years s/p ileocecal pouch, and one adolescent was 5 years s/p ileal bladder augmentation. In all patients the levels of vitamins A, B1, B2, B6, D, and E and of folic acid, bile acid, and ammonia as well as the red blood cell count were within normal ranges. In children (n = 51) there was no significant drop in vitamin B12 levels after the operation. In adults (n = 86), serum vitamin B12 levels dropped significantly from 402 +/- 182 ng/l during the first 2 years after the operation to 292 +/- 204 ng/l after the 4th year (normal range 240-1,100 ng/l). No significant increase in the intracorpuscular vitamin B12 level was observed during the same period. The bone mineral density was normal in all 25 patients with different types of urinary diversion. In addition to regular examination (sonography, creatinine levels, and base excess), vitamin B12 levels should be determined at 4 years after urinary diversion. It remains unclear whether substitution is necessary. However, substitution is easy to achieve and cheaper than the regular determination of vitamin B12. No decrease in bone mineral content was seen in the long-term follow-up with early correction of the base excess (below -2.5).

Withdrawal of Parathyroid Hormone Treatment Causes Rapid Resorption of Newly Formed Vertebral Cancellous and Endocortical Bone in Old Rats

When administered intermittently, parathyroid hormone (PTH) is a strong anabolic agent, increasing both bone mass and bone mechanical strength and competence. This study evaluates the fate of PTH-induced bone in vertebral bodies after withdrawal of PTH treatment in normal old rats. Sixty-seven 21-month-old male rats were treated with 62 μg/kg/day PTH(1–34) for 8 weeks, followed by saline or bisphosphonate (risedronate, 5 μg/kg twice a week) for another 8 weeks. The rats were scanned by dual-energy X-ray absorptiometry at intervals. The bone mineral content (BMC) of L2–5 increased by 33% during the PTH treatment. The BMC started decreasing shortly after withdrawal of PTH and continued to decline during the 8 weeks after withdrawal of PTH. Risedronate, however, prevented this decrease in BMC. All rats were labeled with tetracycline and calcein 3 weeks and 1 week before the cessation of PTH therapy. In the cancellous bone, PTH increased the mineralized surface: 32.9% ± 2.8% (mean ± standard error of the mean) vs. controls 12.0% ± 1.5%, the mineral appositional rate (0.65 ± 0.02 to 0.88 ± 0.06 μm/day), and the cancellous bone volume (BV/TV: 14.5% ± 0.7% to 27.5% ± 1.7%). Withdrawal of PTH induced a fast and pronounced bone resorption, decreasing both the extent of the fluorochrome labels and the cancellous bone volume to control values. Risedronate prevented this resorption. In the cortical bone of the vertebral shell, PTH induced large increases in the endocortical mineralized surface, mineral appositional rate, and cortical area. The endocortical fluorochrome labels were, however, resorbed after withdrawal of PTH. Risedronate maintained both the fluorochrome labels and the cortical area. At the periosteum, the response to PTH was less evident, however, and hardly any labeling was seen at the periosteum facing the vertebral canal either in the controls or in the PTH-treated rats. The compressive strength of the vertebral body specimens increased with PTH treatment whether measured in newtons (317 ± 23 to 623 ± 54 N), normalized to cross-sectional area (23.0 ± 1.4 to 44.7 ± 2.5 N/mm 2), or to ash content per millimeter height (58 ± 2 to 76 ± 2 N × mm/mg). Withdrawal of PTH decreased the compressive strength and competence to control values. Risedronate, however, maintained the PTH-induced mechanical strength and competence. The study discloses that even in very old rats withdrawal of PTH treatment causes a rapid and pronounced decline in the bone mass deposited during PTH treatment; treatment with risedronate can, however, maintain the PTH-induced bone properties in the axial skeleton of old rats.

Bone changes after 3 mo of lactation: influence of calcium intake, breast-milk output, and vitamin D-receptor genotype

Factors influencing the change in bone mineral after 3 mo of lactation were investigated in 47 breast-feeding mothers, 11 formula-feeding mothers, and 22 nonpregnant, nonlactating control subjects. At 6-8 wk postpartum, the breast-feeding group had a mean (+/-SD) calcium intake of 34.8+/-13.2 mmol/d and breast-milk volume, calcium concentration, and calcium output of 0.865+/-0.230 L/d, 7.41+/-1.25 mmol/L, and 6.41+/-2.00 mmol/d, respectively. There was no relation between calcium intake and any breast-milk variable. Dual-energy X-ray absorptiometry of the whole body, spine, hip, and forearm was performed at 0.5 and 3 mo. There were significant decreases in bone mineral content at the spine (3.96%; 95% CI: 4.86%, 3.06%), femoral neck (2.39%; 95% CI: 3.61%, 1.17%), total hip (1.51%; 95% CI: 2.45%, 0.60%), and whole body (0.86%; 95% CI: 1.29%, 0.43%) in breast-feeding mothers but not in formula-feeding mothers or nonpregnant, nonlactating women. These changes were not related to calcium intake, breast-milk calcium concentration, vitamin D-receptor genotype, postpartum weight change, or use of the progesterone-only contraceptive pill. After adjustment for bone area, breast-milk volume and height were identified as significant predictors at the spine, such that greater decreases were associated with taller mothers (P = 0.007) and those with greater breast-milk volume (P = 0.001). This finding suggests that the marked bone mineral changes observed in breast-feeding mothers represented a physiologic response to lactation that was independent of dietary calcium supply.

Follow-up of school-age children with bronchopulmonary dysplasia

Objective: To investigate the outcome of school-age children with bronchopulmonary dysplasia (BPD) in terms of nutrition, pulmonary function, and intelligence, and to compare the results with a preterm cohort matched for gestational age and birth weight, and with a term control group. Design: Cross-sectional. Setting: Follow-up clinic at level III neonatal intensive care unit, university-affiliated hospital, Children's Hospital. Subjects: Twelve children who had BPD as infants and 2 control groups of 12 children each. Main outcome variables: Anthropometric measurements, dietary intake, resting energy expenditure, pulmonary function, body composition measurements by dual energy x-ray absorptiometry, and Weschler intelligence test scores. Results: Children with BPD had decreased forced expiratory volume at 1 second, decreased forced expiratory flow between 25% and 75% of vital capacity, and decreased maximal expiratory flow velocity at 50% of vital capacity compared with age-matched normal inborn subjects ( p = 0.025, p = 0.005, and p = 0.0013, respectively). Both children with BPD and matched preterm control children were shorter than infants in the term control group ( p = 0.018). There were no significant differences in the other anthropometric parameters studied. The groups did not differ in resting energy expenditure. Lean body mass was lower in the BPD group compared with the term control groups ( p = 0.017). Bone mineral content was lower in the BPD group compared with both the preterm and term control infants ( p = 0.050 and p = 0.059, respectively). The mean performance intelligence quotient (IQ) and full-scale IQ scores in the BPD group were lower than in the term control group ( p = 0.011 and p = 0.029, respectively). The proportion of children with borderline or intellectually deficient scores was significantly higher in the preterm group compared with the term group for verbal, performance, and full-scale IQ scales ( p = 0.046, p = 0.018, and p = 0.048 respectively). The proportion of children with BPD who had borderline or deficient performance IQ scores was higher than for the term group ( p = 0.046). Conclusions: The lower height and intelligence scores in children with BPD may be related to prematurity and perinatal events rather than pulmonary disease. Subclinical pulmonary dysfunction in children with BPD persists at school age. The lower amount of lean body mass and possible decrease in bone mineral content in children with BPD may be related to their smaller size.

Effect of disuse on bone mineral content, lean mass, and fat mass in osteoarthritic patients

Purpose: To evaluate the effect of disuse on bone mineral content (BMC), lean mass, and fat mass.Method and subjects: We obtained BMC, lean mass, and fat mass from measurements of each side of the arm and the leg in 20 women with unilateral hip osteoarthritis and 63 normal women using a whole-body dual-energy X-ray absorptiometry (DXA) scan. The ratio of the affected side to the unaffected side (A-U ratio) was calculated for BMC, lean mass, and fat mass in the arm and the leg.Results: A significant intergroup difference in the A-U ratio was noted for leg BMC (0.85vs 0.99,P<0.01), and for lean mass of the leg (0.88vs 0.99,P<0.01). When leg BMC was adjusted with lean mass, this intergroup difference became insignificant.Conclusion: This study reconfirmed that a decrease in BMC and lean mass can result from disuse. We suggest that a large portion of BMC loss in the immobilized leg might be a secondary change resulting from lean mass loss.

Changes in Bone Mineral Content in Male Athletes

To determine changes in bone mineral content (BMC) in male athletes, to examine the mechanisms of changes, and to evaluate the effects of intervention. Dual-energy x-ray absorptiometry (DEXA) tests were administered over a 2-year period, and calcium loss during training was determined by analysis of sweat and urine. Calcium supplementation was administered during year 2. SETTING--A midsouth university. Eleven members of a college Division I-A basketball team. Based on observed calcium loss, athletes received differential levels of calcium supplementation. Intervention commenced the week prior to the fall training season and continued through postseason play. MAIN OUTCOME MEASURE--Changes in BMC. Total body BMC decreased 3.8% from preseason to midseason of year 1 (mean decrease, 133.4 g, P = .02), increased nonsignificantly by 1.1% (mean increase, 35.3 g, P = .22) during the offseason, but decreased an additional 3.3% during summer months when practices resumed (mean decrease, 113.1 g, P = .01). Dermal calcium loss averaged 247 mg [corrected] per training session. From preseason to late summer, there was an overall decrease of 6.1% in total BMC and a 10.5% decrease in BMC of the legs. Calcium supplementation was associated with significant increases in BMC and lean body mass. Bone loss is calcium related and exercise is positively related to BMC provided that calcium intake is sufficient to offset dermal loss.