Biomedical subjects

G C Nicholson

Publications and source records attributed to G C Nicholson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Oral contraceptives and bone mineral density: A population-based study.

OBJECTIVE: We sought to test the hypothesis that exposure to oral contraceptives protects the skeleton. STUDY DESIGN: Multiple regression techniques were used to analyze data for a random sample of 710 Australian women (age range, 20-69 years). Bone mineral density was measured at the lumbar spine, proximal femur, whole body, and distal forearm. Oral contraceptive exposure was assessed by a questionnaire. RESULTS: Women exposed to oral contraceptives had a 3.3% greater mean bone mineral density adjusted for body mass index and age at the lumbar spine (partial r (2) = 0.009; P =.014). Adjusted mean vertebral bone mineral density was 3.3% greater for premenopausal women (partial r (2) = 0.008; P <.05), but the effect did not reach significance among postmenopausal women. Higher bone mineral density was associated with increased duration of exposure, with a mean increase of 3.2% associated with the first 5 years and a further 0.2% with >/=5 years of exposure. No association was detected at other sites. CONCLUSION: Exposure to oral contraceptives may be associated with higher lumbar spine bone mineral density.

Absorptiometry, Photon↗

PubMed2000

Calcium intakes among Australian women: Geelong Osteoporosis Study.

BACKGROUND: Dietary calcium deficiency may be a risk factor for osteoporosis. AIMS: To estimate habitual calcium intakes and prevalence of calcium supplementation among free-living Australian women and validate a calcium-specific food-frequency questionnaire. METHODS: Calcium intakes for 1045 randomly selected women (20-92 years) were estimated by questionnaire which was tested against estimates from four day weighed records kept by 32 randomly selected women. RESULTS: The mean difference between calcium estimates was not statistically significantly different from zero (mean difference=121 mg; standard deviation of differences=357 mg; p>0.05). There was moderate agreement (weighted kappa=0.4) between methods in ranking subjects into tertiles of calcium intake. Mean dietary calcium intakes were 615 mg/day for 20-54 years, 646 mg/day for 55-92 years and 782 mg/day for lactating women. Seventy-six per cent of women aged 20-54 years, 87% of older and 82% of lactating women had intakes below the recommended dietary intake (RDI). There was no association detected between calcium intake and age. Dairy foods provided 79.0% of dietary calcium intake. Calcium supplements were used by 6.6% and multivitamins by a further 4.3% of women. Supplementation was independent of dietary calcium intake and more likely used by postmenopausal women. CONCLUSIONS: Our results suggest that 76% of women consume less than the RDI even when supplemental calcium is included. Furthermore, 14% have less than the minimal requirement of 300 mg/day and would, therefore, be in negative calcium balance and at risk of bone loss. Despite advertising campaigns promoting better nutrition and increased awareness of osteoporosis, many women are failing to achieve an adequate calcium intake.

Adult↗

PubMed2000

Prevalence of osteoporosis in Australian women: Geelong Osteoporosis Study.

To evaluate the prevalence of osteoporosis at various sites among Australian women, cross-sectional bone mineral density (BMD) data for adult females was obtained from an age-stratified population-based sample (n = 1494; 20-94 yr) drawn at random from the Barwon Statistical Division, a population characteristic of Australia. Age- and weight- (and for three sites, height) matched reference ranges for BMD at the lumbar spine, proximal femur, forearm, and total body were developed using regression techniques. The cutoff BMD level for osteoporosis at the PA spine was 0. 917g/cm(2) and 0.713 g/cm(2) at the femoral neck according to the World Health Organization (WHO) guidelines. The upper cutoff level for osteopenia was 1.128 g/cm(2) at the PA spine and 0.913g/cm(2) for the femoral neck. The proportion of Australian women categorized as having osteoporosis at the PA spine, femoral neck, or midforearm ranged from 0.9% among those aged 40-44 yr to 87.0% for those older than 79 yr. This study provides reference data representative of the Australian female population. A large proportion of elderly Australian women has osteoporosis according to the WHO guidelines.

Absorptiometry, Photon↗

PubMed2000

Induction of osteoclasts from CD14-positive human peripheral blood mononuclear cells by receptor activator of nuclear factor kappaB ligand (RANKL).

Osteoclasts are bone-resorbing cells that are derived from haemopoietic precursors, including cells present in peripheral blood. The recent identification of RANKL [receptor activator of nuclear factor (NF)-kappaB ligand], a new member of the tumour necrosis factor ligand superfamily that has a key role in osteoclastogenesis, has allowed the in vitro generation of osteoclasts in the absence of cells of the stromal/osteoblast lineage. Human peripheral blood mononuclear cells (PBMC) cultured in vitro with soluble RANKL and human macrophage colony-stimulating factor form osteoclasts. However, PBMC are heterogeneous, consisting of subsets of monocytes and lymphocytes as well as other blood cells. As the CD14 marker is strongly expressed on monocytes, the putative osteoclast precursor in peripheral blood, we have selected CD14(+) cells from PBMC to examine their osteoclastogenic potential and their expression of novel members of the tumour necrosis factor superfamily involved in osteoclastogenesis. Highly purified CD14(+) cells demonstrated mRNA expression of receptor activator of NF-kappaB, but no expression of RANKL or osteoprotegerin, whereas PBMC expressed mRNAs for all three factors. CD14(+) (but not CD14(-)) cells cultured on bone slices for 21 days with human macrophage colony-stimulating factor and soluble RANKL generated osteoclasts and showed extensive bone resorption. Similar numbers of osteoclasts were generated by 10(5) CD14(+) cells and 10(6) PBMC, but there was significantly less intra-assay variability with CD14(+) cells, suggesting the absence of stimulatory/inhibitory factors from these cultures. The ability of highly purified CD14(+) cells to generate osteoclasts will facilitate further characterization of the phenotype of circulating osteoclast precursors and cell interactions in osteoclastogenesis.

Bone Resorption↗

PubMed1999

Expression of functional RANK on mature rat and human osteoclasts.

Although the important roles of RANK/RANKL in osteoclastogenesis have been established, their roles in the regulation of mature osteoclasts remain uncertain. Microisolation has been used to obtain pure populations of rat and human osteoclasts for RT-PCR analysis. RANK and calcitonin receptor mRNA was detected in all the samples whereas OPG and ALP mRNA was not present in any. RANKL mRNA was detected in two of eight rat and one of four human samples. Treatment of osteoclasts with soluble RANKL resulted in translocation of NF-kappaB to the nucleus and elevation of cytosolic and nuclear calcium levels. We have shown that RANK is highly expressed in mature osteoclasts and that its stimulation by RANKL results in activation of NF-kappaB and calcium signalling.

Animals↗

PubMed1999

Health burden of hip and other fractures in Australia beyond 2000. Projections based on the Geelong Osteoporosis Study.

OBJECTIVE: To calculate the expected increase in the number of fractures in adults attributable to the predicted increase in the number of elderly Australians. DATA SOURCES: All fractures in adult residents (> or = 35 years) of the Barwon Statistical Division (total population, 218,000) were identified from radiological reports from February 1994 to February 1996. The Australian Bureau of Statistics supplied predictions of Australia's population (1996 to 2051). MAIN OUTCOME MEASURE: The projected annual number of fractures in Australian adults up to 2051 (based on stable rates of fracture in each age group). RESULTS: The number of fractures per year is projected to increase 25% from 1996 to 2006 (from 83,000 fractures to 104,000). Hip fractures are projected to increase 36% (from 15,000 to 21,000) because of a substantial rise in the number of elderly aged 85 years and over. Hip fractures are expected to double by 2026 and increase fourfold by 2051. CONCLUSIONS: In contrast to Europe and North America, where numbers of hip fractures are expected to double by 2026 and then stabilise, in Australia hip fractures will continue to place a growing demand on healthcare resources for many decades. These projections can be used for setting goals and evaluating the costs and benefits of interventions in Australia.

Adult↗

PubMed1999

Fra-1 potentiates osteoclastic differentiation in osteoclast-macrophage precursor cell lines.

c-Fos, a component of the dimeric transcription factor AP-1, is necessary for osteoclast formation. To determine whether c-Fos can substitute for any or all of the stimuli needed for osteoclast induction, we infected osteoclast precursors with retroviral vectors expressing c-Fos or the Fos-related protein, Fra-1. The infected cells were incubated with or without osteoclast-inductive stimuli. Osteoclast formation from retroviral-infected precursors remained completely dependent on osteoclast-inductive stromal cells. Unexpectedly, infection of bipotential osteoclast-macrophage precursor cell lines with retroviruses expressing Fra-1 but not c-Fos caused a 10-100-fold increase in the number of precursors that developed calcitonin receptors associated with an increase in bone resorption. These observations suggest that, in the precursor cell lines, Fra-1 is a limiting factor for full responsiveness to the osteoclast-inductive environment. Fra-1 is therefore likely to play a role in osteoclast differentiation which is distinct from that of c-Fos.

Autoradiography↗

PubMed1999

Femoral neck dimensions are unlikely to be associated with age at menarche.

Hip axis length (HAL) has been reported as an independent risk factor for hip fracture. Later puberty may increase bone size because of delayed epiphyseal fusion. We sought to identify associations between bone size at the proximal femur with age at menarche and other indices of growth such as stature. Femoral neck dimensions were measured from dual-energy X-ray absorptiometry scans of the proximal femur in a random sample of 203 premenopausal Caucasian women (age 20-30 years). There were no associations between age at menarche and HAL, femoral axis length (FAL) or femoral neck width (FNW). Age at menarche was associated with height (r = 0.2, p = 0.02). Variations in HAL, FAL and FNW do not appear to be related to age at menarche.

Absorptiometry, Photon↗

PubMed1999

Age- and gender-specific rate of fractures in Australia: a population-based study.

There is little population-based data concerning fracture rates in Australia. We ascertained all fractures occurring during 2 years in adults aged 35 years and over residing within a defined region (population 218 000), representative of the Australian population. The major strength of this study is the comprehensive ascertainment of fractures, which was ensured by regular searches of the only two radiologic providers in the Geelong Osteoporosis Study region. Nevertheless, vertebral fractures are likely to be underestimated since our ascertainment relied on a clinical indication for a medical imaging procedure. Among those aged 35-55 years, the fracture rate (persons per 10,000/year) in men was about double the rate in women (65 vs 35). The fracture rate was almost 7 times higher in women over 60 years versus women less than 55 years of age. In contrast, the fracture rate in men over 60 years was only 50% higher than in men less than 55 years of age (72 vs 104). Fracture rates in women and men were highest at the hip (28 and 10 respectively), spine (21 and 7), distal forearm (Colles') (18 and 4) and humerus (11 and 3), and were 3-4 times higher in women than men. These fractures accounted for 63% of all fractures in women and 32% in men. By contrast, the rate of lower leg and ankle fractures was less than 10 per 10,000 in both women and men and did not increase to the same extent with age. Hip fracture rates appear high, particularly among the older age strata, compared with retrospective ascertainment in other populations. In Australia, as in many other countries, there is an increasing longevity of the population. The number of women aged 90 years and over increased by 32% and the number of men of this age increased by 48% in the 5 years between the Australian national census of 1991 and 1996. Given stable fracture rates, the substantial health burden imposed by age-related fractures, particularly hip fractures, will continue to escalate in both women and men.

Adult↗

PubMed1999

Dietary composition affects regional body fat distribution and levels of dehydroepiandrosterone sulphate (DHEAS) in post-menopausal women with Type 2 diabetes.

OBJECTIVE: To compare effects of a high carbohydrate (high-CHO) and a monounsaturated fat diet (high-MUFA) on body fat distribution and sex hormones in post-menopausal women with Type 2 diabetes. DESIGN: Randomised cross-over with no washout. SETTING: Geelong Hospital outpatient. SUBJECTS: Thirty four women were recruited, 30 completed the study, and data are presented for 21 women compliant to the high-CHO diet. INTERVENTIONS: Women followed a high-CHO diet (20% energy (%E) from fat, 60%E from carbohydrate and a high-MUFA diet (40%E from fat, half as monounsaturated fat, 40%E from carbohydrate) in random order for 12 weeks each. MAIN OUTCOME MEASURES: Dietary compliance was measured by change in linoleic acid (C18:2,omega-6) in plasma cholesteryl esters. Body composition was measured by dual-energy X-ray absorptiometry. Fasting concentrations of glucose and insulin were measured in plasma. Steroid hormones and sex hormone binding globulin (SHBG) were measured in serum. RESULTS: On the high-CHO diet C18:2,omega-6 in plasma cholesteryl esters declined by 5.4% (95% confidence intervals (CI), -2.5% to -8.4%, P=0.0015). Fat was lost mainly from the lower body (lower body loss -0.71 kg, 95%CI, -0.43 to -1.00 kg, P=0.001; upper body loss -0.15 kg, 95%CI, -0.76 to +0.46 kg, P=0.6). Yet on the high-MUFA diet, lower body fat loss was minimal (-0.22 kg, 95%CI, +0.11 to -0.55 kg, P = 0.2). By general linear modelling (GLM), differences in lower body fat loss were significantly related to diet (P = 0.04). After adjustment for age, dehydroepiandrosterone sulphate (DHEAS) concentrations after the high-CHO diet were related to levels of lower body fat (r = 0.394, P = 0.04). CONCLUSIONS: In women with Type 2 diabetes following a high-CHO diet for 12 weeks the disproportionate loss of lower body fat is related to a decline in DHEAS.

Adipose Tissue↗

PubMed1999

Identification of incident fractures: the Geelong Osteoporosis Study.

BACKGROUND: Complete fracture ascertainment is critical for fracture cost estimates and planning for future health care facilities. Virtually complete ascertainment is possible for hip fractures because they nearly always require hospitalisation. AIMS: To validate the use of radiological reports as a resource for ascertaining fracture cases, using hip fracture as a model. METHODS: Hip fracture rates obtained from radiological reports were compared with rates obtained from hospital discharge summaries of medical records using International Classification of Diseases-9 (ICD-9) codes 820.0-820.9 and 733.1 over a three-year period. RESULTS: Hip fracture cases numbered 589 using radiological reports and 585 using medical records. Discharge summaries failed to identify 15 cases ascertained through radiology reports whereas 11 cases ascertained through medical records were not identified from X-ray reports. The age-specific incidence rates for radiological ascertainment were within the 95% confidence limits of the rates derived from medical records. CONCLUSIONS: Among a population of patients generally admitted to hospital for treatment of their fracture, we were able to identify more cases from radiological reports than from medical records. Incidence rates for hip fracture were comparable using the two methods. Radiological reports provide a valuable resource for identifying incident fractures. This method of case ascertainment would be suitable for identifying both major and minor fractures in regions with self-contained health services where access to all radiological reports is possible.

Adolescent↗

PubMed1998

Gemfibrozil treatment increases low-density lipoprotein particle size in Type 2 diabetes mellitus but does not alter in vitro oxidizability.

The aim of this study was to determine the effect of the lipid modifying agent gemfibrozil on lipid and coagulation risk factors in patients with Type 2 diabetes mellitus (Type 2 DM). Twenty-six subjects with Type 2 DM and dyslipidaemia were treated for 24 weeks with either gemfibrozil 600 mg orally twice daily or placebo in a double-blind randomized trial. Lipid profiles, fibrinogen, Factor VII, and plasminogen activator inhibitor-1 (PAI-1) were measured by routine laboratory methods. Low density lipoprotein (LDL) size was determined by gradient gel electrophoresis and the resistance of LDL to copper-induced oxidation was assessed by measuring absorbance at 234 nm. Gemfibrozil significantly reduced total cholesterol (-0.9 (-0.48, -1.32) mmol l(-1); p < 0.05) and triglycerides (-2.7 (-1.55, -1.35) mmol l(-1); p < 0.001) vs placebo. The fall in triglyceride was reflected by a fall in VLDL cholesterol levels in the gemfibrozil treated group vs placebo (-1.31 mmol l(-1); p < 0.001). LDL-cholesterol level did not change but LDL particle size increased by 0.5 nm (0.01, 0.93); P < 0.02. The increase in particle size was inversely correlated with the change of triglyceride level (r = -0.79, p < 0.0001) but did not result in any reduction of susceptibility to copper-induced oxidation. There were no significant changes in the coagulation parameters studied. Because of its ability to correct the lipid abnormalities associated with Type 2 DM particularly hypertriglyceridaemia, gemfibrozil provides a useful therapeutic option in the management of diabetic dyslipidaemia but it does not alter in vitro oxidizability of LDL.

Blood Coagulation↗

PubMed1998

Evidence that failure of osteoid bone matrix resorption is caused by perturbation of osteoclast polarization.

Osteoclasts resorb bone by a complex dynamic process that initially involves attachment, polarization and enzyme secretion, followed by their detachment and migration to new sites. In this study, we postulated that mineralized and osteoid bone matrix signal osteoclasts differently, resulting in the resorption of mineralized bone matrix only. We, therefore, compared the cytoplasmic distribution of cytoskeletal proteins F-actin and vinculin using confocal laser-scanning microscopy in osteoclasts cultured on mineralized and demineralized bone slices and correlated the observations with their functional activity. Our results have demonstrated significant differences in F-actin and vinculin staining patterns between osteoclasts cultured on mineralized bone matrix and those on demineralized bone matrix. In addition, the structural variations were accompanied by significant differences in bone resorbing activity between osteoclasts grown on mineralized bone matrix and those on demineralized bone matrix after 24 h of culture --resorption only occurring in mineralized bone but not in demineralized bone. These results indicated that failure of osteoid bone resorption is caused by perturbation of osteoclast polarization.

Actins↗

PubMed1998

Osteoclasts from human giant cell tumors of bone lack estrogen receptors.

Although estrogen is important in human skeletal homeostasis, the major target cell in bone is unknown. Estrogen receptors (ER) have been demonstrated in osteoblasts and bone marrow stromal cells, but their presence in osteoclasts remains controversial because completely pure preparations have not been available. We have examined expression of ER-alpha and ER-beta messenger RNA (mRNA) by RT-PCR in samples from human giant cell tumor of bone (GCT), including: whole tumor, cultured mononuclear cells, and a pure osteoclast population obtained by microisolation. Whole tumor expressed both ER-alpha and calcitonin receptor (CTR) mRNA and apparently lower levels of ER-beta mRNA. Passaged cultures of tumor mononuclear stromal cells also expressed ER-alpha and low ER-beta but not CTR mRNA. In pure preparations of microisolated osteoclasts, expression of ER-alpha or ER-beta mRNA was not detected, whereas expression of CTR mRNA was readily identified. Microisolated GCT mononuclear cells expressed ER-alpha, but no detectable CTR mRNA. Fluorescence in situ hybridization (FISH) using an ER-alpha riboprobe demonstrated strong signal in the mononuclear cells but multinucleated osteoclasts showed no detectable signal. In contrast, CTR mRNA was detected in multinucleated osteoclasts but not in stromal-like tumor cells by FISH. 17Beta-estradiol consistently showed no effect on bone resorbing activity of osteoclasts from GCT cultured on cortical bone, although calcitonin was a potent inhibitor. These findings indicate that significant expression of ER does not occur in osteoclasts derived from human GCT and suggest that estrogen effects are mediated by other cells of the bone environment.

Bone Neoplasms↗

PubMed1998

The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study.

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either "low" or "high" trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual-energy X-ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean +/- SEM) were reduced in both the low and high trauma groups, respectively: spine-posterior-anterior (-0.50 +/- 0.05 and -0.21 +/- 0.08), spine-lateral (-0.28 +/- 0.06 and -0.19 +/- 0.10), femoral neck (-0.42 +/- 0.04 and -0.26 +/- 0.09), Ward's triangle (-0.44 +/- 0.04 and -0.28 +/- 0.08), trochanter (-0.44 +/- 0.05 and -0.32 +/- 0.08), total body (-0.46 +/- 0.06 and -0.32 +/- 0.08), ultradistal radius (-0.47 +/- 0.05 and -0.42 +/- 0.07), and midradius (-0.52 +/- 0.06 and -0.33 +/- 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age-adjusted odds ratio for osteoporosis (t-score < -2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

Absorptiometry, Photon↗

PubMed1997

Complex shape changes in isolated rat osteoclasts: involvement of protein kinase C in the response to calcitonin.

The cytoplasmic spreading of osteoclasts has been used to assess responsiveness to agents such as calcitonin and associated signal transduction mechanisms. Although cyclic AMP and intracellular calcium are known mediators of calcitonin effects in osteoclasts, the role of protein kinase C (PKC) is less clear. We have used time-lapse videomicroscopy of isolated rat osteoclasts to characterize shape changes induced by calcitonin, forskolin, and phorbol 12-myristate-13-acetate (PMA) in the absence and presence of PKC blockers. Treatment with calcitonin reduced cytoplasmic plan area but increased perimeter length, resulting in a characteristic "stellate" appearance, whereas forskolin produced "nonstellate" contraction. The response of osteoclasts to PMA was dose dependent. High concentrations (10(-7)-10(-6) M) produced biphasic responses with transitory, calcitonin-like "stellate" contraction followed by sustained expansion, whereas low concentrations (10(-11)-10(-9) M) produced expansion only. The effects of low-concentration PMA could be prevented by pretreatment with a PKC blocker, whereas the effects of high concentrations were only partially inhibited. The effects of forskolin were unchanged by pretreatment with the PKC blocker. Treatment with calcitonin in the presence of various PKC blockers resulted in paradoxical transient expansion followed by contraction. These results indicate that calcitonin-induced shape change in osteoclasts is a complex process involving protein kinase C in addition to cyclic AMP-dependent mechanisms and possibly other factors.

Analgesics↗

PubMed1997

Relationship of serum leptin to total and truncal body fat.

1. In this study we investigated the relationship between serum leptin levels and body fat distribution in a random sample of women of widely ranging age and body mass index. Anthropometry and dual energy X-ray absorptiometry were used to measure body fat and its distribution. 2. Leptin levels (log transformed) were not significantly correlated with age, but were significantly positively correlated (P < 0.001) with most anthropometric measures except waist-to-hip circumference ratio. The strongest correlations were with total grams of body fat and percentage body fat (r = 0.68 and 0.76 respectively, P < 0.001). When corrected for percentage body fat the partial correlation coefficients for all other measures became non-significant. The correlation with truncal body fat fell significantly from 0.66 to -0.05 after correction, but the partial correlation with total body fat remained significant (P < 0.005) when grams of truncal fat were controlled for (r = 0.21). 3. These results indicate that the relationship of serum leptin to percentage body fat is the strongest, and that truncal body fat, although the most metabolically active, does not appear to have an independent association with serum leptin.

Absorptiometry, Photon↗

PubMed1997

Parathyroid hormone-related protein-(107-139) inhibits bone resorption in vivo.

PTH-related protein-(107-139) [PTHrP-(107-139)] has been reported previously to be a potent inhibitor of osteoclast activity. However, this finding has not been reproduced in other in vitro models. We have now examined the effects of this peptide in an in vivo model, employing intact adult mice. Four groups of eight male mice were given injections of either vehicle or one of three doses of PTHrP-(107-139) (4 x 10(-13), 4 x 10(-11), or 4 x 10(-9) mol) over the periosteum of the right hemicalvaria for 5 consecutive days. The animals were killed 1 week after the last injection. There were significant decreases in bone resorption indexes after all doses of PTHrP-(107-139), with a 70% decrease in osteoclast number (P < 0.001), a 70% decrease in osteoclast perimeter (P = 0.004) and a 50% decrease in eroded perimeter (P = 0.001). In addition, some indexes of bone formation were significantly decreased, with 40% decreases in both osteoblast number (P = 0.05) and osteoblast perimeter (P = 0.02), but no significant change in osteoid area. There was a dose-related upward trend in mineralized bone area, reaching 12% at the highest dose, but this was not statistically significant. It is concluded that PTHrP-(107-139) is a potent inhibitor of bone resorption in vivo. As this model is very dissimilar to that of isolated osteoclasts, in which this peptide is also active, the present findings suggest that osteoclast inhibition is an authentic action of the C-terminus of PTHrP, which may, therefore, play a role in the regulation of bone turnover in vivo.

Animals↗