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PubMed1990

Prolonged and ubiquitous inhibition by interferon gamma of bone resorption induced by parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, and interleukin 1 in fetal mouse forearm bones.

To investigate the mechanism of the inhibitory effects of interferon-gamma (IFN-gamma) on bone resorption, the effects of murine IFN-gamma on 45Ca release from prelabeled fetal mouse forearm bones were investigated. Murine IFN-gamma usually did not affect basal 45Ca release but almost completely and equipotently inhibited bone resorption induced by PTH(1-34), PTH-rP(1-34), 1,25(OH)2D3, and interleukin 1 (IL-1). The half-maximal concentration for inhibition of bone resorption induced by IL-1 alpha was 25.8 +/- 14.6 U/ml (mean +/- SD for 13 experiments), which is not different from those for PTH, PTH-rP, and 1,25(OH)2D3. There was no correlation between prostaglandin E2 concentration in the conditioned medium and 45Ca release from the IFN-gamma-treated forearm bones. The inhibitory effect of IFN-gamma on bone resorption induced by PTH-rP (1-34) or IL-1 alpha continued during 6 days of culture, whereas that of calcitonin disappeared after 2 days of culture. These findings suggest that IFN-gamma non-preferentially inhibits bone resorption induced by various bone-resorbing factors in fetal mouse forearm bones via a PGE2-independent mechanism. As no escape phenomenon developed in IFN-gamma-treated bones, the cytokine may be potentially useful for treatment of certain patients with malignancy-associated hypercalcemia.

Animals↗
PubMed1991

Serum triiodothyronine, bone turnover, and bone mass changes in euthyroid pre- and postmenopausal women.

Hyperthyroidism and thyroid hormone substitutive therapy with serum iT3 in the normal range of values are known to lead to increased bone remodeling and loss of bone mass. We looked for a relationship between serum iT3 and bone metabolic or bone mass parameters in 402 euthyroid women aged 44-60. In a group of 93 premenopausal women, a group of 309 postmenopausal women, and a group of 118 untreated postmenopausal women, serum iT3 was higher in the women classified as having "high" bone turnover according to both alkaline phosphatases and hydroxyprolinuria values. In postmenopausal women, serum iT3 corrected for thyroid binding globulin (TBG) (T3c) was higher in those receiving no estrogen replacement therapy. In a longitudinal study (n = 131), the rate of changes in lumbar bone mineral content was associated with changes in T3c. A less favorable bone mass evolution was associated with an increase in serum T3c, and inversely. Data suggest that the relationship of iT3/bone metabolism is direct and not merely the consequence of estrogen induced changes in both iT3 and bone metabolism. iT3 should be explored at the bone cellular level as a possible mediator in bone metabolic changes occurring in menopause and many other clinical situations.

Adult↗
PubMed1988

Temporal relationship between bone loss and increased bone turnover in ovariectomized rats.

To characterize osteopenic changes in ovariectomized (OVX) rats as a function of time, female Sprague Dawley rats (240 g body weight, 90 days old) were subjected to bilateral ovariectomy or sham surgery and killed at various times from 14-180 days postovariectomy. The proximal tibial metaphysis was processed undecalcified for quantitative bone histomorphometry. Osteopenia and increased indices of bone resorption and formation were detected in OVX rats as early as 14 days. Longitudinal bone growth was also significantly increased by ovariectomy at 14 days, but returned to control levels at all later times. In OVX rats, osteopenia became progressively more pronounced with time up to 100 days postovariectomy, after which trabecular bone volume appeared to stabilize at the markedly reduced level of 5%. Changes in osteoclast surface, osteoblast surface, and fluoro-chrome-based indices of bone formation in OVX rats followed a similar time course. The maximal increase in these parameters occurred during the first several months postovariectomy followed by a gradual decline toward control levels. Our results indicate that the initial rapid phase of bone loss in OVX rats is coincident with the maximal increase in bone turnover. At later times postovariectomy, bone loss and bone turnover both subside. These findings emphasize the close temporal association between the development of osteopenia and increased bone turnover in OVX rats.

Animals↗
PubMed2001

Combined use of bone and bone marrow scintigraphies for the diagnosis of active sacroiliitis: a new approach.

Diagnosis of sacroiliitis (SI) with bone scintigraphy may involve difficulties even with a quantitative approach. The aim of this study was to evaluate the combined use of bone and bone marrow scintigraphies for the diagnosis of active sacroiliitis. Thirty-one patients who were clinically suspected to have SI were included in the study. Bone and bone marrow scintigraphies were done after injections of 740 MBq of 99mTc-MDP (MDP) and 370 MBq of 99mTc-sulfur colloid (SC) respectively with a 2-day interval. Both visual and quantitative assessment of MDP uptake and visual assessment of SC uptake in sacroiliac joints were performed. Also sacroiliac joint radiographic findings for each patient were evaluated and graded from 0 to 4 according to the New York grading system. Patients were divided into 2 groups according to their x-ray findings (Group A: grade 0-2, Group B: grade 3-4). A total of 14 patients (10 bilateral, 4 unilateral) had increased MDP uptake with decreased/normal SC uptake. Twelve of 14 patients had grade 0-2 radiographic changes while only 2 patients had grade 3-4 radiographic changes. Increased MDP uptake with decreased/normal SC uptake is the most common scintigraphic pattern seen in acute phase SI in which radiographic findings are generally found to be normal or slightly changed. In at least in 8 patients the decreased bone marrow uptake of SC was demonstrated, supporting the diagnosis. Although our results did not reveal any significant superiority of bone marrow scintigraphy to bone scan for the detection of active sacroiliitis, combined use of bone and bone marrow scintigraphies was presented as an alternative method to characterize patients with active sacroiliitis.

Adult↗
PubMed2001

Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency.

Serum bone-Gla protein (BGP), bone alkaline phosphatase (B-AP), and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels were evaluated in 18 adults with acquired GH deficiency (GHD, 14 males and 4 females, age range: 25-59 yr) before, at 3, 6, 9 and 12 months of rec-GH treatment (0.125 IU/kg/week for the first month, followed by 0.25 IU/kg/week for 11 months) and 6 months after the withdrawal of therapy. Total body bone mineral density (BMD, g/cm2) was measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) before, at 12 months of GH treatment and 6 months after its withdrawal. Before treatment, BGP (mean+/-SE: 5.1+/-0.4 ng/ml), B-AP (59.4+/-6.5 IU/l), ICTP (3.1+/-0.3 ng/ml) levels of patients were similar to in healthy controls (BGP: 5.4+/-0.1 ng/ml; B-AP: 58.2+/-2.0 IU/l; ICTP: 4.1+/-0.3 ng/ml). GH treatment caused a significant increase of BGP, B-AP, ICTP levels, the maximal stimulation of bone resorption, occurring after 3 months of GH treatment, while the maximal effect on bone formation being evident later (at 6th month). A slight decline in BGP, B-AP, T-AP and ICTP levels occurred at 9-12 months of therapy, although the values remained significantly higher than in basal conditions and with respect to healthy controls. Before treatment, mean total body BMD of patients (1.110+/-0.027 g/cm2, range: 0.944-1.350 g/cm2) was not significantly different (z-score: +0.47+/-0.31, NS) from that observed in healthy controls (1.065+/-0.008 g/cm2, range: 1.008-1.121 g/cm2). GH therapy was associated with a significant reduction of mean total body BMD values (6th month: -1.8+/-0.5%, p<0.01; 12th month: -2.1+/-1.0%, p<0.05 vs baseline), particularly evident in the first six months of treatment. Six months after the withdrawal of GH therapy, BGP (5.9+/-0.5 ng/ml), B-AP (57.3+/-7.0 IU/l) and ICTP (3.2+/-0.1 ng/ml) levels returned similar to those recorded before treatment, while total BMD increased (+1.5+/-0.7, p<0.05), remaining however slightly lower than in basal conditions (-0.6+/-1.2, NS). In conclusion, our study shows that: a) acquired GHD in adulthood is associated with both normal bone formation/resorption indexes and normal total body BMD; b) GH therapy causes a significant rise of bone formation/resorption markers (earlier and greater for bone resorption); c) one-year GH therapy is associated with a reduction of total body BMD values, particularly evident in the first 6 months of treatment; d) the effects of GH therapy on bone turnover are transient, being completely reverted six months after the withdrawal of GH therapy; e) the increase of total body BMD (up to baseline values) after GH withdrawal might be explained as consequence of persisting effects of previous GH stimulation on bone remodeling.

Absorptiometry, Photon↗
PubMed2003

Aging bone in men and women: beyond changes in bone mineral density.

Using peripheral quantitative computed tomography (pQCT) we assessed trabecular and cortical bone density, mass and geometric distribution at the tibia level in 512 men and 693 women, age range 20-102 years, randomly selected from the population living in the Chianti area, Tuscany, Italy. Total, trabecular and cortical bone density decreased linearly with age ( p<0.0001 in both sexes), and the slope of age-associated decline was steeper in women than in men. In men, the cortical bone area was similar in different age groups, while in women older than 60 years it was significantly smaller by approximately 1% per year. The total cross-sectional area of the bone became progressively wider with age, but the magnitude of the age-associated increment was significantly higher in men than in women ( p<0.001). The minimum moment of inertia, an index of mechanical resistance to bending, remained stable with age in men, while it was significantly lower in older compared with younger women (0.5% per year). The increase in bone cross-sectional area in aging men may contribute to the maintenance of adequate bone mechanical competence in the face of declining bone density. In women this compensatory mechanism appears to be less efficient and, accordingly, the bone mechanical competence declines with age. The geometric adaptation of increasing cross-sectional bone size is an important component in the assessment of bone mechanical resistance which is completely overlooked, and potentially misinterpreted, by traditional planar densitometry.

Adult↗
PubMed2006

Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength.

Most studies that have investigated the anabolic effects of parathyroid hormone (1-84) (PTH) or PTH fragments on the skeleton of ovariectomized (OVX) rats have evaluated the short-term effects of high-dose PTH(1-34) in young animals. This study used densitometry, histomorphometry, and biomechanical testing to evaluate the effects of 12-month daily treatment with low-dose PTH (15 or 30 microg/kg) in rats that were 10 months old at baseline, 4 months after OVX. Bone mineral density (BMD) and bone strength were reduced substantially in control OVX rats. The 15 microg/kg dose of PTH restored BMD to levels similar to those in sham animals within 6 months at the lumbar spine, distal and central femur, and whole body and maintained the BMD gain from 6 to 12 months. The 30 microg/kg dose produced greater effects. Both PTH doses normalized the trabecular bone volume-to-total volume ratio (BV/TV) at lumbar vertebra 3 but not at the proximal tibia (where baseline BV/TV was very low), solely by increasing trabecular thickness. PTH dose-dependently increased bone formation by increasing the mineralizing surface, but only the 30 microg/kg dose increased resorption. PTH increased cortical BMD, area, and thickness, primarily by increasing endocortical bone formation, and restored all measures of bone strength to levels similar to those in sham animals at all skeletal sites. PTH increased bone mass safely; there was no osteoid accumulation, mineralization defect, or marrow fibrosis and there were no abnormal cells. Thus, long-term PTH therapy normalized bone strength in the aged OVX rat, a model of postmenopausal osteoporosis, through increased bone turnover and enhanced formation of both trabecular and cortical bone.

Absorptiometry, Photon↗
PubMed1999

Bone density, vitamin D status, and disordered bone remodeling in end-stage chronic liver disease.

Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease (CLD). The aim of this study was to determine the relative contribution of increased resorption and decreased formation to hepatic osteodystrophy by measuring biochemical markers. Twenty-seven patients with advanced CLD (14 female, 13 male) were enrolled. Bone mineral density (BMD), measured at the lumbar spine, and femoral neck, were measured by dual energy X-ray absorptiometry (DXA); bone turnover was assessed using biochemical markers of bone formation and resorption. Based on WHO criteria, osteoporosis and osteopenia were present in 41% and 18% of patients, respectively. All three markers of bone resorption (free deoxypyridinoline, pyridinoline, and hydroxyproline) were increased significantly in patients with CLD. There was a less marked change in the markers of bone formation (osteocalcin, procollagen type 1 peptide, and bone alkaline phosphatase), resulting in a negative uncoupling index in 23/27 (85%) of the patients. Only two (7%) patients had biochemical changes consistent with osteomalacia. The results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and therapeutic strategies should be designed to suppress bone resorption, especially in preparation for liver transplantation. Bone biomarkers may be useful alternatives to bone biopsy in evaluating hepatic osteodystrophy.

Absorptiometry, Photon↗
PubMed1990

Separation of non-collagenous proteins of bone formed in titanium implants: experimental study in the rabbit tibia, using a bone harvest chamber.

The non-collagenous proteins of mature cortical rabbit bone and 3 wk old bone specimens formed in titanium implant bone harvest chambers, were separated by means of fine pressure liquid chromatography. It was found that a sufficient amount of bone could be obtained from five bone harvest chambers in five rabbits during a period of 15 wk. A different protein chromatographic pattern was found in bone grown in bone harvest chambers as compared to normal cortical bone from the same region. This indicates a difference in bone quality and shows that this implant design can be used for biochemical analysis of bone formed adjacent to a biomaterial.

Animals↗
PubMed1990

Leukemia inhibitory factor (LIF) inhibits basal bone resorption in fetal rat long bone cultures.

Leukemia inhibitory factor (LIF) has a wide variety of biologic actions. In vivo, its net effect on bone is to increase new bone formation. Recently, the sequence of human LIF was found to differ by only a single amino acid from that of human differentiation-inducing factor (D-factor). The effects of LIF on bone appear to be complex since purified murine D-factor and recombinant LIF stimulate bone resorption in cultured newborn mouse calvaria. To examine further the responses of bone to LIF, we studied the effects of recombinant human LIF (glycosylated and nonglycosylated) and recombinant human D-factor (non-glycosylated) on resorption in another in vitro organ culture model, fetal rat long bones. Both LIF preparations and D-factor inhibited basal bone resorption rates by 25% to 44% in these cultures. Resorption rates in maximally inhibited LIF-treated cultures were similar to those in devitalized bones. Inhibitory effects typically occurred at concentrations of greater than or equal to 10 ng/mL (0.5 nM) for the non-glycosylated LIF and D-factor and 1000 U/mL for glycosylated LIF. Neither LIF nor D-factor blocked the resorptive response to interleukin 1 (IL 1) or parathyroid hormone (PTH) nor did they alter total DNA synthesis. Hence, their inhibitory effects appeared to be specific for the mechanisms regulating basal resorptive activity. These results demonstrate that LIF has potent inhibitory actions on basal resorption rates in these cultures. These effects may be important for the anabolic responses that LIF has on bone in vivo. In addition, they may also be involved in the interactions between inflammatory or tumor cells and bone.

Animals↗
PubMed1986

Effect of ethane-1-hydroxy-1,1-diphosphonate on ectopic bone formation induced by murine osteosarcoma-derived bone-inducing substance.

The effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on ectopic bone formation were studied qualitatively and quantitatively in an experimental system for ectopic bone formation induced by murine osteosarcoma-derived bone-inducing substance. At a low dose of EHDP (3 mg/kg per day i.p.), histologic sequelae of ectopic bone formation were normal, and the size of the induced bone mass was unaffected. At a high dose of EHDP (30 mg/kg per day i.p.), an unmineralized bone matrix with hematopoietic bone marrow was formed without evidence of retardation. This osteoid tissue showed no radiologic and histologic evidence of mineralization during the period of EHDP administration. When EHDP was withdrawn, its inhibitory effect on mineralization was reversed. The induced bone mass was almost the same size as that in controls. These results suggest that EHDP might not prevent ectopic bone matrix formation, but its mineralization and withdrawal of EHDP might lead to the formation of a normal bone similar in size to that formed without EHDP treatment.

Animals↗
PubMed1988

Different roles for calcium and cyclic AMP in the action of PTH: studies in bone explants and isolated bone cells.

In fetal mouse calvaria forskolin (0.1-100 microM), like PTH, stimulated cyclic AMP production in a dose-dependent way. The dose-response curve for forskolin-induced bone mineral release (24 hrs), however, demonstrated a biphasic character, showing stimulation at 0.1 microM and inhibition at 5 and 10 microM. In addition, forskolin-stimulated bone resorption reached a plateau after 48 hrs of incubation, a phenomenon which did not occur with PTH. Forskolin (0.1 microM) strongly stimulated PTH-induced cyclic AMP production in fetal mouse calvaria. However, PTH-stimulated bone resorption and PTH-induced increase in cytosolic free Ca2+ in bone fetal rat cells were not stimulated by forskolin (0.1 microM). 9-(Tetrahydro-2-furyl) adenine (100 microM) completely blunted PTH-stimulated cyclic AMP response in fetal mouse calvaria. PTH-stimulated bone resorption was also completely inhibited, but only after 6 hrs and not after 24 hrs of incubation. With nifedipine and varabamil PTH-stimulated bone resorption was significantly inhibited after 24 hrs of incubation and not significantly after 6 hrs of incubation. A23187 (1 microM) significantly stimulated PTH-stimulated cyclic AMP level and increased basal cytosolic free Ca2+ concentration in cultured rat bone cells. In calvaria, however, it had no effect on either basal and PTH-stimulated cyclic AMP production or on basal and PTH-stimulated bone resorption (6 and 24 hrs). From these observations it follows that in calvaria manipulation of intracellular cyclic AMP only (partially) affects bone resorption. This observation points to a role for an additional second messenger in establishing full blown bone resorption. Some of the results are published in short elsewhere.

Animals↗
PubMed1989

Skeletal fluorosis: histomorphometric analysis of bone changes and bone fluoride content in 29 patients.

Bone fluoride content (BFC) was measured and histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores from 29 patients (16 men, 13 women, aged 51 +/- 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either hydric (endemic or sporadic) or industrial, or in a few cases iatrogenic. Measured on calcined bone using a specific ion electrode, BFC was significantly high in each specimen (mean +/- SD; 0.79 +/- 0.36% on bone ash). The radiologically evident osteosclerosis observed in each patient was confirmed by a significant increase in cancellous bone volume (40.1 +/- 11.2% vs. 19.0 +/- 2.8% in controls, p less than 0.0001). There were significant increases in cortical width (1292 +/- 395 mcm vs. 934 +/- 173 mcm, p less than 0.0001) and porosity (14.4 +/- 6.4% vs. 6.5 +/- 1.7%, p less than 0.002), but without reduction of cortical bone mass. Cancellous osteoid volume and perimeter, as well as width of osteoid seams, were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost three-fold greater than that noted in cancellous eroded perimeter. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, mineralization lag time was significantly increased. The fluorotic group had a greater number of osteoblasts than controls with a very high proportion of flat osteoblasts. The ultrastructural characteristics reflecting the activity of the bone cells were clearly visible on electron microscopy. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. On stained sections and microradiographs, bone tissue showed typical modifications for skeletal fluorosis (linear formation defects, mottled bone). The volume of cancellous interstitial mineralization defects and the proportion of mottled periosteocytic lacunae were markedly increased in skeletal fluorosis. These two parameters were significantly correlated together but neither of these was significantly correlated with BFC. Renal function did not significantly influence the changes in BFC and histomorphometry of fluorotic patients. Skeletal fluorosis is thus characterized by an unbalanced coupling in favor of bone formation, and a great number of osteoblasts with a high proportion of flat osteoblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMedDate not supplied

Maintaining restored bone with bisphosphonate in the ovariectomized rat skeleton: dynamic histomorphometry of changes in bone mass.

This experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an antiresorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE2/kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE2 treatment and began treatment with 1 or 5 micrograms/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the proximal tibial metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE2 treatment was stopped, the PGE2-induced cancellous bone disappeared. In contrast, 5 micrograms of Risedronate inhibited the bone loss and maintained it at the PGE2 treatment level. The key dynamic histomorphometry value for the restore (R) and maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 microgram Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5 micrograms Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE2 after discontinuing PGE2 by administering enough Risedronate, a resorption inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Differences in axial bone mineral density, serum levels of sex steroids, and bone metabolism between postmenopausal and age- and body size-matched premenopausal subjects.

The present study was designed to investigate the differences in serum levels of sex steroids, bone metabolism, and bone mineral density (BMD) between 22 premenopausal subjects and 21 age- and body size-matched postmenopausal subjects. Dual photon absorptiometry (DPA) demonstrated total body BMD significantly decreased in postmenopausal subjects. It was also found that not only spinal BMD as assessed by DPA, but also total third lumbar BMD and third lumbar trabecular BMD as measured by quantitative computed tomography (QCT) significantly decreased in these subjects. In postmenopausal subjects, the urinary-hydroxyproline/creatinine ratio increased significantly, which suggested that bone resorption had been stimulated, and serum levels of alkaline phosphatase (ALPase) and osteocalcin also significantly increased, which suggested a stimulation of bone formation. Consequently, the reduction in BMD was thought to result from a negative balance of bone resorption versus bone formation, or a high turnover of bone metabolism. Androgens were not confirmed to participate in these changes in bone metabolism, but the reduction in serum levels of estradiol, as a major factor, and the reduction in serum levels of estrone, as a participating factor, were assumed to result in an increase in bone resorption in excess of bone formation.

Absorptiometry, Photon↗
PubMed1996

High bone turnover is associated with low bone mass in both pre- and postmenopausal women.

In 979 healthy women, aged 30-75 years, bone mass was measured by DXA in the lumbar spine and proximal femur, and by SXA in the distal forearm. Bone turnover was assessed by urinary CrossLaps (CrossLaps ELISA), a new assay which measures type I collagen degradation products in urine and by osteocalcin (two-site N-Mid hOsteocalcin ELISA), a new assay which measures the N-terminal-mid fragment (1-43) as well as the intact (1-49) osteocalcin (OCN-Mid) in serum. For comparison data on urinary hydroxyproline (fU Hpr/Cr) and serum, total alkaline phosphatase were included (AP). In premenopausal women below 50 years of age, the concentrations of the biochemical markers were stable with age. At menopause CrossLaps and OCN-Mid increased abruptly to a level 60% and 35% above the premenopausal mean values (p < 0.001). Premenopausal women in the highest quartiles, stratified according to the concentration of CrossLaps and OCN-Mid corrected for height and weight, had 6%-11% lower bone mass in all regions (p < 0.01) as compared to women in the lowest quartiles. CrossLaps and OCN-Mid corrected for height and weight correlated with bone mass in the spine and proximal femur, r = -0.13 to r = -0.28, p < 0.05. In postmenopausal women, the difference in bone mass between the highest and lowest quartiles was 8%-14% (p < 0.001). CrossLaps and OCN-Mid correlated with bone mass measured in all regions, r = -0.14 to r = -0.32, p < 0.05. The correlation between bone mass and AP and Fu Hpr/Cr was lower; r = -0.06 to r = -0.20 for premenopausal women, NS to p < 0.01, and r = -0.01 to r = -0.23, NS to p < 0.001 for postmenopausal women. In conclusion, the present data indicate that high bone turnover is associated with a significantly lower bone mass in not only postmenopausal, but interestingly also in premenopausal women. In consistence with previous results, we found that bone turnover increased perimenopausally and in the early menopause.

Adult↗
PubMed2006

Renal insufficiency-induced bone loss is associated with an increase in bone size and preservation of strength in rat proximal femur.

Chronic renal insufficiency (CRI) results in phosphate retention and secondary hyperparathyroidism, the treatment of which is largely based on the use of calcium salts as phosphate binders. Advanced CRI causes bone fragility, but information about bone geometry and strength in moderate CRI is scarce. We assigned 39 8-week-old male Sprague-Dawley rats to sham-operation (Sham) or 5/6 nephrectomy (NTX). Four weeks later, the rats were randomized to 0.3% calcium (Sham, NTX) or 3.0% calcium diet (Sham + Calcium, NTX + Calcium). After 8 weeks, the animals were sacrificed, plasma samples collected, and femora excised for neck and midshaft analyses: dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and biomechanical testing. The NTX increased plasma urea and PTH 1.6-fold and 3.6-fold, respectively, whereas high calcium intake suppressed PTH to 30% of controls. Total femoral bone mineral content decreased (-6.3%) in the NTX group, while this deleterious effect was reversed by high calcium diet. In the site-specific analysis of the femoral neck, the volumetric bone density (-6.5%) was decreased in the NTX group but not NTX + Calcium group. However, in the nephrectomized rats, there was also a concomitant increase in the cross-sectional area (+15%), and, despite the decrease in bone density, the mechanical strength of the femoral neck was maintained. In the midshaft, NTX decreased cortical volumetric bone density (-1.2%), but similar to the femoral neck, no differences were found in the mechanical strength. In conclusion, a decrease in bone mass in moderate experimental CRI was associated with a concomitant increase in bone size, and maintenance of mechanical competence. Although high calcium diet suppressed plasma PTH to under normal physiological levels, it prevented the CRI-induced loss of bone mass without an adverse influence on bone strength.

Absorptiometry, Photon↗
PubMed2005

Evolution of mechanoregulation of bone growth will lead to non-optimal bone phenotypes.

Mechanical forces acting on the bones during growth affect their final shape and strength. Mechanoregulation of bone growth may be recognized in embryogenesis, and also in the adaptation of the adult skeleton to changes in mechanical loading. Mechanoregulatory responses for tissues have arisen during evolution, but does evolution give rise to responses that produce optimal skeletal phenotypes? In this paper, we investigate the emergence of an optimal mechanoregulation response in a population. By combining equations describing long bone growth with a genetic algorithm to describe evolutionary change, we created a computational model to simulate the evolution of mechanoregulation in bone growth. A population of individuals is created where each individual is assigned a diploid gene set which controls the growth and remodelling of the bone. At maturity, each bone is assessed and its 'fitness' calculated; fitness is quantified as bone strength relative to bone mass. The simulation continues for many generations, and includes mutations and a varying environment. The genes present in the population are tracked and the evolution of parameters governing mechanoregulation is calculated. The results indicate that a population may converge to one bone growth algorithm but, more usually, a range of mechanoregulation algorithms for different individuals will persist after many generations. Even if the population converges to one mechanoregulation law, convergence to the 'optimum' bone was never found. Although many researchers propose that natural selection has pushed skeletal structure towards an optimum, our computational model suggests that this is unlikely to be the case.

Adaptation, Physiological↗