Differences In Bone Resorption Research Articles

Systemic administration of propranolol reduces bone resorption and inflammation in apical periodontitis of chronically stressed rats.

To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats. Twenty-four 70-day-old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal-Wallis followed by Dunn's test. Significance level was set at 5% (p < .05) for all assessed parameters. Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05). Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.

Curcumin reduces inflammation in rat apical periodontitis.

The aim of the study was to evaluate the effect of systemic curcumin administration on the severity of apical periodontitis (AP). Forty male Wistar rats weighing 250-280 g each, age 2.5months, were distributed into four groups (n=10): control untreated rats (C), control rats treated with curcumin (CUR), rats with pulp exposure-induced apical periodontitis (AP) and rats with pulp exposure-induced apical periodontitis treated with curcumin (AP-CUR). Curcumin treatment was administered orally once daily for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed at 30 days, and the jaws were collected and reconstructed in a programme specific for micro-CT. The jaws were processed for analysis of the inflammatory process using haematoxylin and eosin staining and immunohistochemical assays for interleukin tumour necrosis factor alpha (TNF-α), interleukin (Il)-6 and Il-1β. Tartrate-resistant acid phosphatase (TRAP) and osteocalcin (OCN) staining were used to analyse the resorptive process on the bone surface of periapical area. Kruskal-Wallis with Dunn's test was performed for nonparametric data and anova with Tukey's test for parametric data, p< .05. Micro-CT revealed no statistically significant differences in bone resorption between the AP and AP-CUR groups (p > .05). The levels of inflammatory cell infiltration and immunoreactivity for the proinflammatory cytokines TNF-α, Il-6 and Il-1β were significantly higher in the periapical lesions of the AP group than in the AP-CUR group (p < .05). The number of TRAP-positive multinucleated cells was higher in the AP group than in the AP-CUR group (p < .05). In OCN-positive cells, no differences were observed between the AP and AP-CUR groups (p > .05). Oral supplementation with curcumin had a significant effect on the AP severity in rats, suggesting an anti-inflammatory effect of curcumin on AP development.

Cytokines, Adipokines, and Bone Markers at Rest and in Response to Plyometric Exercise in Obese vs Normal Weight Adolescent Females.

BackgroundIn adults, excess adiposity has been associated with low-grade, chronic inflammation and compromised bone health, but less is known about these linkages in children. The purpose of this study was to compare the circulating levels of inflammatory cytokines, adipokines, osteokines, and bone markers at rest and in response to plyometric exercise between obese and normal weight adolescent females.MethodsTen normal weight (BMI = 21.3 ± 2) and 10 obese (BMI = 32.9 ± 4), postmenarcheal females, aged 13–17 years, performed one bout of plyometric exercise (5 circuits; 120 jumps). Blood samples were taken at rest, 5 min, 1 h, and 24 h post-exercise. Tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), insulin, leptin, osteocalcin, carboxy-terminal telopeptide (CTX), sclerostin, and parathyroid hormone (PTH) were measured in serum.ResultsCytokines were not different between groups at rest or over time with IL-6 increasing (+31%; p = 0.04) 5 min post-exercise and TNF-α decreasing (-9%; p = 0.001) 1 h post-exercise. Insulin and leptin were higher in the obese compared to the normal weight females. In both groups, insulin significantly increased 5 min post-exercise but remained elevated 1 h post-exercise only in the obese group. Leptin did not change in response to exercise. Osteocalcin was lower in the obese group across time and increased (+12%; p = 0.02) 24 h post-exercise in both groups. CTX was similar between groups at rest and decreased (-24%; p < 0.001) 1 h post-exercise. Sclerostin was similar between groups at rest, but there was a significant interaction reflecting a significant increase (+29%; p = 0.04) 5 min post-exercise in the obese group and a non-significant decrease (-13%; p = 0.08) in normal weight controls. PTH increased 5 min post-exercise, dropped 1 h post-exercise to lower than pre-exercise, and returned to baseline 24 h post-exercise in both groups.ConclusionObese adolescent females from our study had no evidence of resting inflammation or differences in bone resorption but show blunted bone formation when compared to normal weight controls. The direction and temporal changes in inflammatory cytokines, adipokines, and bone turnover markers to exercise were similar in both groups, reflecting an overall bone anabolic response for most biomarkers, except sclerostin, which increased only in the obese females immediately post-exercise, suggesting a different systemic regulation of sclerostin depending on adiposity.

Bone Remodeling Under Screw-Fixed Chin Implants in Patients With Microgenia: A Cross-Sectional Study

The use of alloplastic chin implants has been associated with a risk of bone resorption. The aims of this study were to evaluate, in patients with microgenia, the association between chin implants and bone resorption and identify the associated risk factors for such resorption. The sample consisted of 51 patients with microgenia: 17 with chin implants (group A, placed over the course of a 15-year period [2002-2017]) and 34 without implants (group B). Cone-beam computed tomography was used to evaluate bone erosion in different areas of the chin. The patients were evaluated, and their medical records were reviewed to identify risk factors. A chi-square or Fisher exact test and the Mann-Whitney test were used to compare groups; resorption sites were compared with Friedman test. Linear regression models were used to evaluate associations between potential risk factors and resorption. Bone resorption was higher in group A than in group B (mean ± SD: 0.98 ± 0.63 mm vs 0.03 ± 0.12 mm; P &lt; .0001). Symphyseal buccal cortical bone in group A was thinner (1.66 ± 0.34 mm) than it was in group B (2.07 ± 0.45 mm), P &lt; .001. Group A showed appositional bone growth and no cortical bone perforation. The mean of the amount of bone resorption of chin implant patients compared with that of those without implants was, on average, 0.99 mm greater (95% confidence interval: 0.64-1.35; P &lt; .001). Although statistically significant differences in bone resorption were observed between groups, these differences were not clinically significant. Thinning of symphyseal buccal cortical bone without perforation and appositional bone growth occurred in chin implant patients, suggesting bone remodeling. Our results suggest that bone that is in contact with chin implants remodels and remains stable throughout the years, instead of undergoing progressive resorption.

Survival Rate and Bone Resorption in Immediate Loading of Atrophic Maxillary Arches Using Normal and Long Implants: A Pilot Observational Study.

To estimate implant survival and peri-implant bone resorption around long vs normal-length implants in full-arch immediate loading rehabilitation of maxillary arches of low bone quality (D4). A total of 45 patients received two mesial normal-length (10 to 15 mm) or longer (18 to 20 mm) implants and two long (18 to 20 mm) distally tilted implants. Differences in bone resorption at 24 months were assessed using the Mann-Whitney U Test. At the 24-month follow-up, no significant differences were found in survival (global cumulative survival rate: 98.9%) or bone resorption (mean: 1.1 mm) between long and normal implants (P = .053). At 24 months, the use of long implants provides favorable survival and bone maintenance results in the immediate loading rehabilitation of low-quality maxillary arches.

Influence of Different Surface Characteristics on Peri-implant Tissue Behavior: A Six-Year Prospective Report

The aim of this study was to evaluate the behavior of hard and soft tissue around implants with different surface treatments. Eight patients were identified for this study. Each patient received at least 2 implants (1 control, 1 test) into an edentulous quadrant, for a total of 10 pairs of implants. Two types of implants were used: hybrid implants (control) with a dual acid-etched surface in their apical portion and a machined coronal part, and test implants with an acid-etched surface throughout their entire length. Standardized periapical radiographs were taken at baseline, 3 months, 6 months, and 1 year post implant placement and then annually until the 6-year follow-up. Bleeding on probing (BOP) and Plaque Index (PI) were recorded annually. Probing depth (PD) was recorded at the 6-year follow-up. Moderate crestal bone remodeling was observed during the 1-year postimplant placement evaluation (P=.001), and test implants revealed smaller marginal bone resorption (P=.030). No significant changes in bone level were observed between the 1-year and the 6-year follow-up appointments, and a significantly smaller bone resorption was found at test implants. No statistically significant differences in bone resorption were found between maxilla and mandible. No statistically significant differences were detected between test and control implants for BOP, PI, or PD. The preliminary results suggest that implant surface characteristics might affect the bone remodeling phase subsequent to the surgical trauma. However, once osseointegration was established, implant surfaces did not affect bone maintenance over time. Implant surfaces did not affect soft tissue behavior. The results of this pilot study need to be confirmed in a study with a larger sample size and over a longer time frame.

Changes in Bone Resorption Across the Menopause Transition: Effects of Reproductive Hormones, Body Size, and Ethnicity

Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m² and smallest in women with BMI >30 kg/m². Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.

Low bone turnover and low bone density in a cohort of adults with Down syndrome

Increased incidence of osteoporosis in Down syndrome has been reported, but etiology is not established. We report low bone turnover markers and bone mineral density (BMD) in a cohort of people with Down syndrome without consistent clinical risk factors. Our results should guide future studies and treatments for this common problem. To better understand the etiology for osteoporosis in Down syndrome (DS), we measured bone density by dual-energy X-ray absorptiometry (DXA) and circulating biochemical markers of bone formation and resorption in a cohort of 30 community-dwelling DS adults. Seventeen males and 13 females followed in the University of Arkansas Down Syndrome Clinic were evaluated by DXA to estimate BMD and underwent phlebotomy to measure serum procollagen type-1 intact N-terminal propeptide (P1NP) to evaluate bone formation, and serum C-terminal peptide of type-I collagen (CTx) to evaluate bone resorption. Seven of 13 DS females and 12 of 17 DS males had low bone mass at one of measured sites (z≤-2.0). When data were grouped by age, males had apparent osteopenia earlier than females. The mean P1NP in the normal group was 19.2±5.2 ng/ml vs. 2.2±0.9 ng/ml in the DS group (P=0.002). Serum CTx levels in the normal group were 0.4±0.1 ng/ml vs. 0.3±0.1 ng/ml (P=0.369). Low BMD in adults with DS is correlated with a significant decrease in bone formation markers, compared to controls without DS, and is independent of gender. These data suggest that diminished osteoblastic bone formation and inadequate accrual of bone mass, with no significant differences in bone resorption, are responsible for the low bone mass in DS. These observations question the use of antiresorptive therapy in this population and focus attention on increasing bone mass by other interventions.

Reduced Proliferation and Osteocalcin Expression in Osteoblasts of Male Idiopathic Osteoporosis

Osteoporosis is characterized by low bone mineral density (BMD), resulting in increasing susceptibility to bone fractures. In men, it has been related to some diseases and toxic habits, but in some instances the cause of the primary--or idiopathic--osteoporosis is not apparent. In a previous study, our group compared histomorphometric measurements in cortical and cancellous bones from male idiopathic osteoporosis (MIO) patients to those of control subjects and found reduced bone formation without major differences in bone resorption. To confirm these results, this study analyzed the etiology of this pathology, examining the osteoblast behavior in vitro. We compared two parameters of osteoblast activity in MIO patients and controls: osteoblastic proliferation and gene expression of COL1A1 and osteocalcin, in basal conditions and with vitamin D(3) added. All these experiments were performed from a first-passage osteoblastic culture, obtained from osteoblasts that had migrated from the transiliac explants to the plate. The results suggested that the MIO osteoblast has a slower proliferation rate and decreased expression of genes related to matrix formation, probably due to a lesser or slower response to some stimulus. We concluded that, contrary to female osteoporosis, in which loss of BMD is predominantly due to increased resorption, low BMD in MIO seems to be due to an osteoblastic defect.

Calcium supplementation and bone mineral accretion in adolescent girls: an 18-mo randomized controlled trial with 2-y follow-up

Background:A recent meta-analysis raised doubt as to whether calcium supplementation in children benefits spine and hip bone mineral density (BMD). Objective:We used state-of-the-art measures of bone (fan-beam dual-energy X-ray absorptiometry and 4 bone turnover markers) to determine whether girls with low habitual calcium intake benefited from supplementation with a soluble form of calcium (calcium citrate malate dissolved in a fruit drink). Design:The trial was an 18-mo randomized trial of calcium supplementation (792 mg/d) with follow-up 2 y after supplement withdrawal. Subjects were 96 girls (mean age: 12 y) with low calcium intakes (mean: 636 mg/d). The main outcome measure was change in total-body, lumbar spine, and total hip bone mineral content (BMC) during supplementation and 2 y after supplement withdrawal. Changes in BMD and bone turnover markers were secondary outcome measures. Results:The mean additional calcium intake in the supplemented group was 555 mg/d. Compared with the control group, the supplemented group showed significantly (P < 0.05) greater gains in BMC (except at the total hip site) over the 18-mo study. BMD change was significantly (P < 0.05) greater for all skeletal sites, and concentrations of bone resorption markers and parathyroid hormone were significantly (P < 0.01) lower in the supplemented group than in the control group after 18 mo. After 42 mo, gains in BMC and BMD and differences in bone resorption were no longer evident. Conclusions:Calcium supplementation enhances bone mineral accrual in teenage girls, but the effect is short-lived. The likely mechanism for the effect of the calcium is suppression of bone turnover, which is reversed upon supplement withdrawal.

Accentuated Ovariectomy-Induced Bone Loss and Altered Osteogenesis in Heterozygous N-Cadherin Null Mice

Ovariectomy-induced bone loss is accentuated in mice with germline Cdh2 haploinsufficiency, the result of a decreased osteoblastogenesis in the face of normal osteoclast number. Reduced N-cadherin abundance in these mice decreases cell-cell adhesion and alters signaling pathways important for osteoblast commitment and differentiation, thus providing in vivo evidence that N-cadherin-mediated cell-cell interactions are involved in homeostatic responses to increased bone remodeling. We have shown that targeted expression of a dominant negative truncated form of N-cadherin (Cdh2) delays acquisition of peak bone mass in mice and retards osteoblast differentiation. We tested the role of this molecule in the skeletal homeostatic response to ovariectomy in mice with germline Cdh2 haploinsufficiency. Heterozygous Cdh2 null (Cdh2+/-) and wildtype mice were ovariectomized and followed up to 13 weeks by in vivo radiodensitometric and ex vivo histologic assessment of bone mass and turnover. Cells isolated from wildtype and Cdh2+/- mice were used to determine the alterations in bone cell function produced by partial loss of N-cadherin. Bone mass was not significantly different between Cdh2+/- and wildtype littermates, but on ovariectomy, bone loss in Cdh2+/- mice was initially slower, but with time it became significantly greater than in wildtype mice. This accentuated bone loss was associated with lower osteoblast number and serum osteocalcin levels, with no differences in bone resorption. Although development of calcified nodules was faster in calvaria cells isolated from Cdh2+/- mice relative to Cdh2+/+ cells, bone marrow osteogenic precursors were lower in the former than in the latter genotypes. Cdh2 expression was downregulated with differentiation in wildtype calvaria cells, whereas cadherin-11 abundance remained unchanged. Furthermore, cell-cell adhesion (postconfluence) was decreased among heterozygous calvaria cells, as was cell proliferation (preconfluence), relative to wildtype cells. Finally, the abundance and cellular distribution of beta-catenin was minimally decreased in Cdh2+/- cells, whereas mitogen-activated protein kinase (MAPK) signaling was more active in Cdh2 insufficient cells. Cdh2 is involved in the homeostatic bone formation response to ovariectomy, presumably by regulating osteoprogenitors number and differentiation through stabilization of cell-cell adhesion and/or signaling modulation.

Aspirin, acetaminophen, and ibuprofen: Their effects on orthodontic tooth movement

Orthodontic patients often take analgesics for pain during treatment. But various analgesics have different capacities to inhibit prostaglandins, and these differences might affect tooth movement. The purposes of this study were to determine by direct measurement the effects that acetylsalicylic acid, ibuprofen, and acetaminophen have on orthodontic tooth movement in rats and to evaluate histologically the differences in bone resorption in the pressure area in rats treated with these analgesics. Thirty-six adult male Wistar rats were divided in 4 groups of 9 each. Orthodontic appliances were placed on the rats' incisors. In the 3 experimental groups, analgesics were diluted in reverse osmosis water and delivered via a gastric tube: 100 mg/kg acetylsalicylic acid, or 30 mg/kg ibuprofen, or 200 mg/kg acetaminophen. Control animals received only the reverse osmosis water. At the end of the experimental period, the rats were killed and histological examinations were performed. Analysis of variance showed statistically significant differences between the control group, which was given reverse osmosis water, and the groups given aspirin and ibuprofen. There were also statistically significant differences between the acetaminophen group and the ibuprofen and aspirin groups, respectively. There was no significant difference between the acetaminophen group and the control group, or between the aspirin and ibuprofen groups. Tooth movement was similar in the groups. The results indicate that nonsteroidal anti-inflammatory analgesics such as aspirin and ibuprofen diminish the number of osteoclasts, probably by inhibiting the secretion of prostaglandins, thereby reducing orthodontic tooth movement. Acetaminophen did not affect orthodontic tooth movement in rats, and it might be the analgesic of choice for treating pain associated with orthodontic treatment.

Ein Vergleich der antiresorptiven Effekte von Bisphosphonaten und Statinen auf Polyethylenpartikel-induzierte Osteolysen / A Comparison of the Antiresorptive Effects of Bisphosphonates and Statins on Polyethylene Particle-Induced Osteolysis

An ongoing unraveling of the molecular mechanisms in aseptic loosening of hip arthroplasty has opened up novel potential pharmacological interventions. In this study the antiresorptive effects of the bisphosphonate zoledronate and the statin simvastatin on ultra high molecular weighted polyethylene (UHMWPE) particle-induced osteolysis were compared. Two previous studies of our group based on the murine calvarial model of UHWMPE particle-induced osteolysis were pooled to form four study groups. Animals in group I (n=14) underwent sham surgery only. In groups II (n=14), III (n=7) and IV (n=7) UHMWPE particles were implanted on the calvariae. Animals in groups III and IV were additionally treated with zoledronate (single 25 microg/kg s.c. injection) and simvastatin (120 mg/day p.o. for 14 days), respectively. After two weeks, calvaria were processed for undecalcified histomorphometry. Bone resorption was measured using Giemsa staining. Osteoclast numbers were determined using TRAP-staining. UHMWPE particle implantation resulted in a grossly pronounced osteolytic activity with significantly increased values of bone resorption (p < 0.001) and osteoclast numbers (p < 0.001). Additional treatment with zoledronate or simvastatin counteracted the particle-induced effects. A comparison of the two medical treatments revealed no statistically significant differences in bone resorption (p = 0.63) and osteoclast numbers (p = 0.41). A single dose of the bisphosphonate zoledronate decreased UHMWPE particle-induced osteolysis in a murine calvarial model as effectively as a daily treatment with simvastin. Both drug groups may have a preventive and therapeutic role as antiresorptive agents in wear particle-induced bone resorption following total joint replacement.

Bone resorption in anorexia nervosa and rehabilitated patients.

To assess the impact of anorexia nervosa and that of nutritional rehabilitation on bone resorption. Cross-sectional, observational study. Rome, Italy Twenty-eight female patients affected by anorexia nervosa (AN, BMI<or=17.0 kg/m(2)), 18 females rehabilitated from anorexia nervosa and weight-stable for at least 6 months (RE, BMI >or=18.5 kg/m(2)) and 34 age- and sex-matched healthy controls (CO, BMI >or=18.5 kg/m(2)). Among AN patients, 16 were affected by the 'restrictive' (ANr) and 12 by the 'purging' type (ANp) of anorexia nervosa. Body weight, height and skeletal diameters were measured on each individual. The skeletal mass (SKM) was predicted from the skeletal diameters of the elbow, wrist, knee and ankle, using the equation of Martin. Twenty-four-hour urinary excretion of pyridinium crosslinks of collagen (pyridinoline (Pyd) and deoxypyridinoline (Dpd)) and creatinine was assessed by reversed-phase HPLC with fluorimetric detection after solid-phase extraction and by the Jaffé-method with deproteinization, respectively. Twenty-four-hour urinary output of Pyd and Dpd was not significantly different between AN and CO when expressed in absolute values, but AN showed higher bone resorption than CO when Pyd and Dpd excretion was adjusted by either creatinine (P<0.0000) or the SKM (P<0.05). Within the AN group, urinary excretion of both cross-links was significantly and consistently higher in ANp compared with ANr (P<0.05). However, these differences disappeared when crosslink output was adjusted either by urinary creatinine or SKM. RE subjects showed no differences in bone resorption with the AN group despite weight gain, being crosslink excretion consistently elevated compared to controls (Pyd: P<0.01 by creatinine and P<0.05 by SKM; Dpd: P<0.01 by creatinine and P<0.05 by SKM). Bone resorption is elevated in anorexia nervosa and different strategies for low-weight maintenance do not seem to have a differential impact. Increased bone resorption persists in subjects with past diagnosis of anorexia nervosa despite rehabilitation lasting more than 6 months. This finding indicates that bone mass and turnover should be monitored in anorexia nervosa patients and ex-patients well beyond recovery of normal body mass. Further investigation is warranted to examine the long-term effect of such prolonged increase in bone turnover at a young age.

Skeletal sensitivity to dietary calcium deficiency is increased in the female compared with the male rat

We investigated potential sex differences in bone resorption and the conservation of whole body bone mass in 24-week-old Sprague-Dawley rats maintained on a 1.0% calcium diet and then fed diets containing 0.02, 0.5, 1.0, or 1.75% calcium for 31 days. Lowering dietary calcium from 1.00% to 0.02% doubled whole skeleton bone resorption (urinary 3H-tetracycline loss). Female rats were more sensitive to calcium stress, exhibiting the maximal resorptive response when fed the 0.5% calcium diet, whereas the 0.02% calcium diet was required to elicit this response in males. Despite the evidence of increased bone resorption, whole skeleton mass was unchanged in females and was significantly increased in males, indicating that switching to even the 0.02% calcium diet did not result in an overt loss of total body bone mass. Compared with controls, the skeleton mass of females (97 ± 1.4%) maintained on the 0.02% calcium diet was significantly lower than males (107 ± 2.4%), again suggesting a greater impact of calcium deficiency in females. The calculation of the average percentage growth of selected individual bones in male rats indicated a proportional increase in bone mass between the axial and appendicular skeleton of approximately +4% and +18% in animals maintained on 0.02 and 1.75% diets, respectively. By comparison, female rats consuming the 0.02% calcium diet showed an average 14% loss in axial bone and 7.5% gain in appendicular bone mass. The results indicate increased sensitivity to dietary calcium deficiency in female rats which involves a significant loss in axial bone mass not observed in male rats maintained under similar dietary conditions.Key words: skeleton bone mass, calcium diet, 3H-tetracycline, axial, appendicular, gender, sex.

Differences in bone resorption after menopause in Japanese women with normal or low bone mineral density: quantitation of urinary cross-linked N-telopeptides.

The objective of this study was to examine the value of NTx, a urinary cross-linked N-telopeptides of type I collagen, as a marker of bone resorption. We assessed changes in pre- and postmenopausal bone resorption by evaluating the correlation of NTx with L2-4 bone mineral density (BMD) in a total of 1100 Japanese women, aged 19-80 years [272 premenopausal (45.2 +/- 6.2 years) and 828 postmenopausal (59.5 +/- 6.2 years)]. Postmenopausal women were divided into three groups based on the range of BMD (normal, osteopenic, and osteoporotic). Within each group, subjects were further segregated according to years since menopause (YSM). NTx values were then evaluated for each group. Our results showed that BMD was significantly decreased (P < 0.05) and NTx was significantly increased (P < 0.01) after menopause in age-matched analysis. Consistent with a previous report, NTx was inversely correlated with BMD for the entire cohort of study subjects (r = -0.299), although NTx correlated better with premenopausal than postmenopausal BMD (r = -0.240 versus r = -0.086). This may have been due to the fact that elevated values of NTx were exhibited over the entire range of BMD present in the postmenopausal women, suggesting that NTx might respond faster to the estrogen withdrawal than BMD. In all postmenopausal women, regardless of the range of BMD, the increase in NTx reached a peak within 5 YSM. After 11 YSM, however, NTx remained elevated in the osteoporotic group but it decreased in the osteopenic group, and showed no significant change in the group of postmenopausal women with normal BMD. These findings suggest that bone resorption is dramatically increased within 5 years after menopause but remains increased only in osteoporotic women.

Sex differences in bone resorption in the mouse femur. A light- and scanning electron-microscopic study.

In male and female dd-mice at 4, 7, and 14 weeks of age and in 7- and 14-week-old mice gonadectomized at 4 weeks of age, the number of osteoclasts and the number and size of bone resorption areas along the surface of bone trabeculae in the distal metaphysis of the femur were determined. Osteoclasts were counted at the light-microscopic level in paraffin sections of decalcified femora. The number and size of the bone resorption areas were examined by scanning electron microscopy of femora after removing organic material by means of KOH and NaOCl treatment. In untreated mice, the number of osteoclasts and the number and size of bone resorption areas showed no sex differences at 4 weeks of age but were larger in females than males at 7 and 14 weeks of age. In gonadectomized mice, the number of osteoclasts and the bone resorption areas increased in males and decreased in females. The results of the gonadectomy experiments suggest that bone resorption in young adult mice is stimulated by female sex hormone and inhibited by male sex hormone.

Effects of mithramycin on transplantable canine perianal gland carcinoma (CAC-9) in nude mice: biochemical, histomorphometric, and ultrastructural investigations.

A serially transplantable perianal gland carcinoma (CAC-9) was developed in nude mice from a hypercalcemic dog that has been maintained through passage 20. Tumor doubling rate of CAC-9 was 3.1 +/- 0.4 days. Mithramycin (MMC) injected intraperitoneally (8 mg/kg) into nude mice bearing CAC-9 markedly decreased the tumor volume 2 weeks post-injection. MMC returned the elevated serum and urine calcium levels in mice with CAC-9 back to similar values as controls. The few remaining viable tumor cells after MMC were large and had numerous aggregations of intermediate filaments that displaced cytoplasmic organelles. Histomorphometric evaluation of lumbar vertebrae reveled no significant differences in bone resorption of nude mice bearing CAC-9 compared to saline-treated controls. This rapidly growing tumor line in nude mice associated with mild hypercalcemia will be a useful animal model to evaluate combinations of chemotherapy for cancer-associated hypercalcemia.

Sex differences in bone resorption: A scanning electron microscopic study of mouse parietal bones.

Bone resorption surfaces formed by osteoclasts can be identified as rough areas by scanning electron microscopy (SEM). In this study, the endocranial surfaces of mouse parietal bones were examined by SEM at 1, 4, 6, 8, 14 and 20 weeks of age in an attempt to understand the bone resorbing activity after the cessation of bone growth. On the inner surface of the parietal bones, the rough areas, composed of a group of 8 to 30 microns wide concavities, can be divided into two distinct groups (type I and type II). The surface of type I areas appeared irregularly rough and those of type II revealed feather, fire-flame, or wave-like patterns due to characteristic arrangements of the concavities. The rough areas occupying the inner surface of the parietal bones made up about 60% of the surface area at 1 week and about 5% at 4 weeks in both sexes. The rough areas were all type I at this age. After puberty, the rough areas in males occupied about 10% of the inner surface until 20 weeks and consisted of large type I and small type II areas. In females, the proportion of the rough areas increased after puberty and occupied about 40% of the endocranial surface at 14 and 20 weeks. The type I areas were much larger, increasing in size with age and eventually occupying a large proportion of the rough areas. The sex differences in the rough areas were reversed by gonadectomy. The results suggest that male and female gonadal products, possibly sex hormones, have respective inhibitory and stimulatory effects on the formation of bone resorptive surfaces, and may be responsible for the sex differences in the size and morphological features of the areas on the bone surfaces.