Similar Bone Loss Research Articles

Influence of partially exposed nonabsorbable membrane for alveolar ridge preservation: A randomized controlled trial.

This randomized controlled trial evaluated the impact of a partially exposed non-absorbable membrane (dPTFE) in Alveolar Ridge Preservation (ARP) procedures on clinical, tomographic, immunoenzymatic, implant-related, and patient-centered outcomes. Patients with a hopeless maxillary single-rooted tooth demanding rehabilitation with implants were included. Patients were randomized into two groups: dPTFE (n=22)-tooth extraction followed by ARP using a partially exposed dPTFE membrane; USH (n=22)-unassisted socket healing. Clinical and tomographic analyses were performed at baseline and after 3 months. After 3 months, patients received one dental implant. Implant stability quotient was obtained following implant placement. Bone-related markers were analyzed in bone biopsies using an immunoenzymatic assay. Greater gain in Keratinized Mucosa Width (KMW) was observed in the dPTFE (1.33 ± 0.98 mm) compared to USH (0.59± 0.98 mm) (Mann-Whitney test, Z=2,28, p < 0.05). USH showed a reduction of pain/discomfort, edema, and interference with daily life from the seventh day (Friedman/Wilcoxon test, maxT=7.48, 8.00, and 5.92, respectively, p < 0.05). dPTFE presents a reduction of edema and interference with daily life from the 7th day and pain/discomfort from the 14th day (Friedman/Wilcoxon test, maxT=5.40, 5.26, and 4.78, respectively, p < 0.05). The dPTFE group presented higher pain/discomfort in the 35 and 42 days and higher edema from 7 to 42 days postoperatively than USH group (Mann-Whitney test, p < 0.05). No differences between groups were observed in the tomographic measures, immunoenzymatic analysis, and implant stability (p > 0.05). dPTFE was superior to USH by increasing KMW gain. However, dPTFE without bone graft presented similar bone loss compared to USH. This clinical trial was not registered prior to participant recruitment and randomization (NCT04329351).

Comparison of Marginal Bone Levels Around Tissue-Level Implants with Platform-Matched and Bone-Level Implants with Platform-Switching Connections: 1-Year Results of a Prospective Cohort Study with a Split-Mouth Design.

This clinical study was conducted to compare the influence of a platform-switched bone-level implant and a platform-matched tissue-level implant on marginal bone loss during the first year after loading. Edentulous subjects who applied for two-implant-retained mandibular overdentures and showing sufficient bone volume for implants with 4.3-mm diameter and 12-mm length were enrolled. For standardization reasons, all subjects received a platform-matched tissue-level implant and a platform-switched bone-level implant in the anterior mandible. Since implants from the same manufacturer were used, both implants had identical implant thread designs and surface properties. All subjects received two-implant-retained mandibular overdentures with opposing maxillary complete dentures, and the implants were loaded after 6 weeks. Marginal bone loss was monitored via panoramic radiographs obtained immediately after loading and at the 6- and 12-month recalls after implant loading, and periodontal parameters, such as pocket probing depths, Plaque Index scores, and bleeding on probing, were also measured and recorded. Twenty-six patients received 26 bone-level and 26 tissue-level implants. No statistically significant differences were detected between the bone loss of the two groups for all the measurements (P > .05). Additionally, no significant difference was detected between the measured periodontal parameters of the two groups (P > .05). Within the limitations of this prospective clinical study with a follow-up time of 12 months, it can be concluded that the platform-switching bone-level design and the platform-matching tissue-level design show similar bone loss in the anterior edentulous mandible.

Kindlin-2 mediates mechanotransduction in bone by regulating expression of Sclerostin in osteocytes

Osteocytes act as mechanosensors in bone; however, the underlying mechanism remains poorly understood. Here we report that deleting Kindlin-2 in osteocytes causes severe osteopenia and mechanical property defects in weight-bearing long bones, but not in non-weight-bearing calvariae. Kindlin-2 loss in osteocytes impairs skeletal responses to mechanical stimulation in long bones. Control and cKO mice display similar bone loss induced by unloading. However, unlike control mice, cKO mice fail to restore lost bone after reloading. Osteocyte Kindlin-2 deletion impairs focal adhesion (FA) formation, cytoskeleton organization and cell orientation in vitro and in bone. Fluid shear stress dose-dependently increases Kindlin-2 expression and decreases that of Sclerostin by downregulating Smad2/3 in osteocytes; this latter response is abolished by Kindlin-2 ablation. Kindlin-2-deficient osteocytes express abundant Sclerostin, contributing to bone loss in cKO mice. Collectively, we demonstrate an indispensable novel role of Kindlin-2 in maintaining skeletal responses to mechanical stimulation by inhibiting Sclerostin expression during osteocyte mechanotransduction.

Experimental peri-implantitis around titanium implants with a chemically modified surface with a monolayer of multi-phosphonate molecules: a preclinical in vivo investigation.

The purpose of this experimental in vivo investigation was to evaluate the influence of modifying the implant surface by adding a monolayer of multi-phosphonate molecules on the development of experimental peri-implantitis. Eight beagle dogs received 5 tests and 5 control implants each following a split-mouth design 3months after premolar and molar extraction. On the most mesial implant of each side, a 3-mm buccal dehiscence was artificially created. Experimental peri-implantitis was induced by silk ligatures over a 4-month period; after ligature removal, peri-implantitis was left to progress for another 4months without plaque control. Clinical, histological, and radiographic outcomes were evaluated. Radiographically, both implant groups showed a similar bone loss (BL) at the end of the induction and progression phases. BL measured on the histological sections of the test and control groups was 3.14 ± 0.42mm and 3.26 ± 0.28mm, respectively; the difference was not statistically significant (p > 0.05). The remaining buccal bone to implant contact (bBIC) percentage of the test and control groups was 59.38 ± 18.62 and 47.44 ± 20.46%, respectively; the difference, however, was not statistically significant (p > 0.05). Bone loss observed at dehiscent sites compared to non-dehiscent ones showed no statistically significant difference (p > 0.05). Addition of a monophosphonate layer to a moderately rough implant surface did not affect development of experimental peri-implantitis. Influence of implant surface on peri-implantitis may condition implant selection by the clinician, especially on patients with disease risk factors. In that sense, monophosphate layer implants do not show higher peri-implantitis risk than control implants.

ST2 regulates bone loss in a site-dependent and estrogen-dependent manner.

Interleukin-33 (IL-33) and its receptor, ST2, are implicated in bone remodeling. The lack of estrogen after menopause results in an accelerated bone loss. Here we investigated the role of ST2 in the bone loss induced by estrogen deficiency. ST2-deficient mice (ST2-/- ) and their littermates (wildtype [WT]) were ovariectomized (OVX), while ovary-intact mice were used as controls. Bone sites were analyzed by microcomputed tomography, histomorphometry, and quantitative real-time polymerase chain reaction (qPCR). Deletion of IL-33 or ST2 resulted in a similar bone loss in the femur and maxilla. Ovariectomy in WT mice caused bone loss in the same areas. The lack of ST2 in OVX mice did not alter bone remodeling in the femur but prevented bone loss in the maxilla. Consistently, ovariectomy increased the IL-33 messenger RNA (mRNA) levels in the maxilla but not in the femur. Under mechanical stimulation, ovariectomy and ST2 deletion independently increased bone remodeling induced by orthodontic tooth movement, which was also associated with a greater number of osteoclasts and a reduced number of osteoblasts in the maxillary bone. ST2-/- OVX mice, however, displayed twice as many osteoblasts as that of WT OVX mice. Ovariectomy and ST2 deletion differently altered the cytokine mRNA levels in the maxilla. Remarkably, interleukin-10 expression was decreased in both WT OVX and ST2-/- mice, and this reduction was completely restored in ST2-/- OVX mice. The results demonstrate that estrogen and IL33/ST2 independently protect against bone loss. However, the ovariectomy-induced bone loss is IL-33/ST2-dependent in the maxilla but not in the femur, indicating a bimodal and site-specific role of ST2 in bone remodeling.

Periodontal bone height of exclusive narghile smokers compared with exclusive cigarette smokers

ObjectiveTo compare the periodontal bone height (PBH) of exclusive narghile smokers (ENS) with that of exclusive cigarette smokers (ECS).MethodsTunisian males aged 20–35 years who have been ENS for more than five narghile-years or ECS for more than five pack-years were recruited to participate in this comparative cross-sectional study. Information about oral health habits and tobacco consumption were gathered using a predetermined questionnaire. Plaque levels were recorded in four sites using the plaque index of Loe and Silness. The PBH was measured mesially and distally from digital panoramic radiographs of each tooth and expressed as a percentage of the root length. A PBH level ≤0.70 was applied as a cutoff reference value signifying bone loss. Student t-test and Chi2 test were used to compare quantitative and qualitative data of both groups.ResultsThere were no significant differences between the ENS (n=60) and ECS (n=60) groups regarding age and the consumed quantities of tobacco (28±4 vs. 27±5 years, 7±3 narghile-years vs. 8±3 pack-years, respectively). Compared with the ECS group, the ENS group had a significantly higher plaque index (mean±SD values were 1.54±0.70 vs. 1.84±0.73, respectively). However, the two groups had similar means of PBH (0.85±0.03 vs. 0.86±0.04) and tooth brushing frequencies (1.1±0.8 vs. 0.9±0.6 a day, respectively) and had similar bone loss frequencies (15% vs. 12%, respectively).ConclusionsBoth ENS and ECS exhibited the same PBH reduction, which means that both types of tobacco smoking are associated with periodontal bone loss.

Diminished Progression of Periapical Lesions with Zoledronic Acid in Ovariectomized Rats

IntroductionThe aim of this study was to investigate the effects of systemically administered zoledronic acid (ZOL) on the progression of periapical lesions in estrogen-deficient rats. MethodsFemale Wistar rats were divided into the following groups: SHAM-veh, sham surgery treated with vehicle (physiological saline); OVX-veh, ovariectomy treated with vehicle; SHAM-ZOL, sham surgery treated with ZOL; and OVX-ZOL, ovariectomy treated with ZOL. Vehicle or ZOL was administered intravenously once a week for 4 weeks. The pulp of the mandibular first molar of all rats was exposed to the oral environment to induce a periapical lesion, and the lesions were analyzed after 7 and 30 days. The mandibles were examined by micro–computed tomographic imaging and histopathologic, histometric, and immunohistochemical analyses. ResultsHistopathologically, the OVX-veh group had more severe inflammation and bone loss and a larger number of cells that were positive for tartrate-resistant acid phosphatase compared with the SHAM-veh and OVX-ZOL groups; the SHAM-veh and OVX-ZOL groups were similar to each other. The SHAM-ZOL group had the lowest magnitude of these conditions. Tomographically, the OVX-veh group had greater bone loss than the other groups at both time points. The SHAM-veh, SHAM-ZOL, and OVX-ZOL groups had similar bone loss at both time points. In the sagittal section on day 30, the SHAM-ZOL group had lower bone loss compared with the SHAM-veh and OVX-ZOL groups. ConclusionsThe hypoestrogenic condition aggravates the progression of periapical lesions. ZOL therapy may help contain bone destruction of periapical lesions.

The Use of Technical "Standard All-on-Four" in the Maxilla

Among the factors that should be considered for the rehabilitation of atrophic jaws is mainly the anatomy of edentulous jaw, which offers trouble installing fixtures in view of the proximity to the maxillary sinus and nasal cavity. There are several possibilities to rehabilitate atrophic arcs, autogenous grafts, distraction osteogenesis, angled and short implants have been widely used in clinical practice. Thus, advanced surgical techniques are disclosed in the literature, such as the all-on-four standard technique. This technique consists of inserting implants for a complete rehabilitation, and inclining a previously straight distal implant 45°, allowing anchorage in better bone (jaw previous zones), use of longer implants and decreasing the size of the prosthetic cantilever. The purpose of this literature review was to evaluate the scientific articles who observed the behavior of dental implants installed by the technique in the maxilla. Initially, using the key words, 62 articles were obtained. After applying the inclusion criteria, 19 articles were selected. In each study the following were evaluated parameters: success rate of angled and axial implants, bone loss, and prosthetic complications. Finally, seven studies contemplated the requirements to be in this review. The literature of the art all-on- four standard in edentulous jaws showed that both angulated and axial implants have high success rate (92.8% to 99.3%) and similar bone loss. Therefore, the all-on-four standard technique is a viable option in the medium- and long-term for immediate fixed prosthetic rehabilitation in atrophic jaws.

Implant Survival and Marginal Bone Loss at Turned and Oxidized Implants in Periodontitis‐Susceptible Smokers and Never‐Smokers: A Retrospective, Clinical, Radiographic Case‐Control Study

Little is known about the long-term outcome of oxidized surface oral implants, especially in periodontitis-susceptible smokers. The aim of this study is to determine implant survival and marginal bone loss at turned and oxidized implants in smokers and never-smokers with periodontitis. Forty smokers and 40 never-smokers with experience of advanced periodontal disease, treated with implants 5 years previously, are included in this study. Groups were matched for sex, oral hygiene, and implant distribution, and patients were subgrouped by implant surface type (turned or oxidized). The overall implant survival rate was 96.9% in never-smokers and 89.6% in smokers. Compared with oxidized implants, turned implants failed more frequently in smokers. In smokers, mean (standard error of the mean) marginal bone loss at 5 years was 1.54 (0.21) mm at turned and 1.16 (0.24) mm at oxidized implants. In never-smokers, significantly greater bone loss was found at oxidized implants, 1.26 (0.15) mm, than at turned implants, 0.84 (0.14) mm. Oxidized implants demonstrated similar bone loss for both groups. Turned implants lost significantly more bone in smokers. Compared with never-smokers, the smokers' likelihood ratio for implant failure was 4.68, 6.40 for turned and 0.00 for oxidized implants. The results of the study underscore the need for prevention and cessation of smoking. Turned implants failed more frequently and lost more marginal bone in smokers. In contrast, oxidized implants showed similar failure rates and bone loss in smokers and never-smokers. Turned implants displayed less bone loss than oxidized implants in never-smokers. Oxidized surface implants are more suitable for patients susceptible to periodontitis who smoke.

P17 The H2S-releasing naproxen-derivative ATB-346 inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis

Periodontitis is the result of the extension of gingival inflammation far down the periodontium, thus damaging the structures responsible for tooth-bone insertion, which may subsequently cause tooth loss. Non-steroidal antiinflammatory drugs (NSAIDs) are widely prescribed for control of a variety of inflammatory conditions, although gastric effects limit their use. In experimental periodontitis, NSAIDs also decrease the associated alveolar bone loss. Since the addition of an H2S-releasing moiety to classical NSAIDs result in antiinflammatory compounds with improved gastric safeness [1] , we decided to compare the effects of naproxen with its H2S-releasing derivative ATB-346 (Antibe Therapeutics Inc., Canada) on ligature-induced periodontitis in rats. All animal procedures were approved by the local ICB-USP Ethics Committee. A 3–0 cotton ligature was subgingivally placed around the lower right first molar of male Wistar rats (220–250 g), previously anesthetized with ketamine and xylazine (80 mg/kg and 16 mg/kg, i.p., respectively); sham animals had the ligature removed immediately after the procedure. After ligature placement, groups of animals (n = 8) started to receive daily equimolar oral bolus doses of naproxen (10 mg/kg), ATB-346 (16 mg/kg) or vehicle (1 ml/kg of 0.5% CMC) during the following 7 days; a non-treated group was also included. After this period, the anesthetized animals were euthanized (exsanguination) and the mandibles were collected, X-rayed for alveolar bone loss measurement (distance between the cemento-enamel junction and the alveolar bone crest at the mesial face of the ligatured tooth), and prepared for histological analysis. Samples of stomach and gingiva were also collected for measurement of myeloperoxidase (MPO) activity (a marker of granulocyte infiltration) and interleukin (IL)-1β contents. Data were analyzed by one-way ANOVA followed by the Student-Neuman-Keuls test. Seven days after ligature placement, both untreated or vehicle-treated animals showed similar bone loss (0.94 ± 0.06 and 0.96 ± 0.08 mm, respectively), which was significantly inhibited by either naproxen (0.74 ± 0.06 mm, P These results show that the presence of the H2S-releasing moiety in the ATB-346 compound does not impair the effects of the parent naproxen on periodontitis, but rather prevents the occurrence of deleterious effects on the gastric mucosa due to long-term prostaglandin inhibition. Financial support: CAPES, CNPq, FAPESP.

Mesiodistal Bone Loss of Fresh Socket Placed Implants and Delay Placed Implants at the Anterior of the Maxilla

Introduction: Immediate implant placement in fresh extraction sockets provides the advantage of shorter treatment time along with minimizing the number of surgical interventions. Materials and methods: Subjects were studied in two groups: in group 1, subjects received a fresh socket placed implant at the anterior of the maxilla and in group 2, a delay placed implant was inserted at the same site. The mesial and distal marginal bone level was measured using parallel technique radiography in time 0, 12, 24 and 36 months after loading. Results: Seventy subjects were studied in two groups. Analysis of the data using a repeat measure test demonstrated the similar bone loss patterns between two groups. Time has a significant effect on bone loss in time 1, 2, 3. The amount of bone loss increased as time passed after loading time. Comparison of bone loss in both groups demonstrated that the amount of bone loss in the central site was more than the lateral site in three measurement times for the group 2 but in the group 1, a significant difference was not observed. Conclusion: Comparison of marginal bone loss in fresh socket placed implants and delay implants did not show a significant difference. Also a continuous bone resorption was observed over the time in the both groups. It may be needed to investigate other success criteria in fresh socket placed implants for making an appropriate treatment plane.

Evaluation of Markers of Bone Turnover During Lactation in African-Americans: A Comparison With Caucasian Lactation

The African-American skeleton is resistant to PTH; whether it is also resistant to PTHrP and the hormonal milieu of lactation is unknown. The objective of the study was to assess bone turnover markers in African-Americans during lactation vs Caucasians. A prospective cohort study with repeated measures of markers of bone turnover in 60 African-American women (3 groups of 20: lactating, bottle feeding, and healthy controls), compared with historic Caucasian women. The study was conducted at a university medical center. Biochemical markers of bone turnover and calcium metabolism were measured. 25-Hydroxyvitamin D (25-OHD) and PTH were similar among all 3 African-American groups, but 25-OHD was 30%-50% lower and PTH 2-fold higher compared with Caucasians (P < .001, P < .002), with similar 1,25 dihydroxyvitamin D [1,25(OH)(2)D] values. Formation markers [amino-terminal telopeptide of procollagen-1 (P1NP) and bone-specific alkaline phosphatase (BSAP)] increased significantly (2- to 3-fold) in lactating and bottle-feeding African-American women (P1NP, P < .001; BSAP, P < .001), as did resorption [carboxy-terminal telopeptide of collagen-1 (CTX) and serum amino-terminal telopeptide of collagen 1 (NTX), both P < .001]. P1NP and BSAP were comparable in African-American and Caucasian controls, but CTX and NTX were lower in African-American vs Caucasian controls. African-American lactating mothers displayed quantitatively similar increases in markers of bone formation but slightly lower increases in markers of resorption vs Caucasians (P = .036). Despite reported resistance to PTH, lactating African-American women have a significant increase in markers of bone resorption and formation in response the hormonal milieu of lactation. This response is similar to that reported in Caucasian women despite racial differences in 25-OHD and PTH. Whether this is associated with similar bone loss in African-Americans as in Caucasians during lactation is unknown and requires further study.

Rehabilitation of the Atrophic Posterior Maxilla With Pterygoid Implants: A Review

The purpose of this article is to review the literature published and to assess the success of treatment of patients with atrophic posterior maxilla with pterygoid implants. Studies from 1992 to 2009 on patients with atrophic posterior maxilla rehabilitated with pterygoid implants were reviewed. Those reporting clinical series of at least 5 patients with atrophic posterior maxilla (Class IV and V of Cawood and Howell), rehabilitated with pterygoid implants and fixed prosthesis, and with 12 months minimum follow-up were included. In each study the following were assessed: number of patients, number of implants, surgical technique, prosthetic rehabilitation, success rate, bone loss, complications and patient satisfaction. Thirteen articles were included, reporting a total of 1053 pterygoid implants in 676 patients. The weighted average success of pterygoid implants was 90.7%; bone loss evaluated radiographically ranged between 0 and 4.5 mm. No additional complications compared with conventional implants were found, and patient satisfaction level with the prosthesis was high. Pterygoid implants have high success rates, similar bone loss levels to those of conventional implants, minimal complications and good acceptance by patients, being therefore an alternative to treat patients with atrophic posterior maxilla. Two anatomical locations in which implants are placed in the retromolar area can be distinguished: the pterygoid process and the pterygomaxillary region. Implant lengths and angulations vary between these two techniques.

Reduced methacholine-induced submandibular salivary secretion in rats with experimental periodontitis

ObjectiveSaliva is the first barrier to the entry of bacteria and viruses into the body and is considered a necessary instrument in oral health. Intraperitoneal injection of lipopolysaccharide endotoxins results in submandibular gland (SMG) hyposalivation. The objective of present studies was to assess if periodontitis, a chronic inflammatory disease caused by oral bacteria, alters cholinergic-induced SMG salivary secretion. DesignAn experimental periodontitis model (EP) (cotton thread ligature around the neck of the first lower molars) was used. Male Wistar rats (300–380g) were randomly divided into 3 groups: control, 7 days-bilateral EP and 7 days-unilateral EP (to study if there were different effects at the ipsilateral and contralateral side). The following determinations were performed in SMG: (1) dose–response curves to the cholinergic agonist methacholine, (2) prostaglandin E (PGE) content, (3) inducible nitric oxide synthase (iNOS) activity and (4) histology of gland sections. ResultsThe molars with EP, no matter the group, exhibited significant and similar bone loss (p<0.001). Bilateral EP reduced methacholine-induced salivary secretion (p<0.05, dose 1μg/kg; p<0.001, dose 3–30μg/kg), increased PGE content (p<0.01), stimulated iNOS activity (p<0.05). Ipsilateral glands of unilateral EP animals presented lower methacholine-induced salivary secretion (p<0.05, dose 3μg/kg; p<0.001, dose 10–30μg/kg), and higher PGE content than contralaterals (p<0.001). In turn, at 3 and 10μg/kg of methacholine, contralateral glands showed significantly lower secretion than control animals (p<0.001). Histological studies of glands revealed partial loss of secretor granular material and periductal oedema in the bilateral and unilateral EP groups as compared to controls. ConclusionsAs far as we know, the present results demonstrate for the first time that EP reduces methacholine-induced SMG salivary secretion.

HIV Infection and Bone Loss Due to Periodontal Disease

The goal of this study is to determine whether HIV infection or high-risk behaviors associated with HIV infection are related to alveolar bone loss in a sample of subjects screened at a dental school clinic. Subjects were included in this study (N = 355) if they were HIV positive or had high-risk behaviors associated with HIV infection as identified by health risk behavior screening questionnaire. Bone loss measurements were obtained from radiographs. Both bivariate relationships and multivariate relationships between alveolar bone loss and three sets of variables were evaluated: high-risk behavior questions, demographic variables, and HIV infection. The following variables were found related to alveolar bone loss in bivariate relationships: age (P < or = 0.0001); smoking (pack-years) (P < or = 0.0001); race (P < or = 0.002); gender (P < or = 0.032); male-male sex (P <0.001); diabetes (P < or = 0.015); sharing of needles (P < or = 0.02); and hepatitis C positive (P < or = 0.05). In the multiple regression model, age, smoking, race, gender, and male-male sex remained significant. In both analyses, HIV-positive individuals had similar bone loss compared to those who were HIV negative. These results suggest that HIV infection is not related to alveolar bone loss in individuals with high-risk behaviors for HIV infection. These results also suggest that previously reported relationships between HIV infection and increased alveolar bone loss may be explained by other factors, such as smoking. Individuals in this study population with risk behaviors associated with HIV infection smoked at a high rate and, because of the smoking behavior, have a high rate of periodontal disease.

Increased bone resorption and impaired bone microarchitecture in short-term and extended high-fat diet–induced obesity

Although obesity traditionally has been considered a condition of low risk for osteoporosis, this classic view has recently been questioned. The aim of this study was to assess bone microarchitecture and turnover in a mouse model of high-fat diet–induced obesity. Seven-week-old male C57BL/6J mice (n = 18) were randomized into 3 diet groups. One third (n = 6) received a low-fat diet for 24 weeks, one third was kept on an extended high-fat diet (eHF), and the remaining was switched from low-fat to high-fat chow 3 weeks before sacrifice (sHF). Serum levels of insulin, leptin, adiponectin, osteocalcin, and cross-linked telopeptides of type I collagen (CTX) were measured. In addition, bone microarchitecture was analyzed by micro–computed tomography; and lumbar spine bone density was assessed by dual-energy x-ray absorptiometry. The CTX, body weight, insulin, and leptin were significantly elevated in obese animals (sHF: +48%, +24%, +265%, and +102%; eHF: +43%, +52%, +761%, and +292%). The CTX, body weight, insulin, and leptin showed a negative correlation with bone density and bone volume. Interestingly, short-term high-fat chow caused similar bone loss as extended high-fat feeding. Bone volume was decreased by 12% in sHF and 19% in eHF. Bone mineral density was 25% (sHF) and 27% (eHF) lower when compared with control mice on low-fat diet. As assessed by the structure model index, bone microarchitecture changed from plate- to rod-like appearance upon high-fat challenge. Trabecular and cortical thickness remained unaffected. Short-term and extended high-fat diet–induced obesity caused significant bone loss in male C57BL/6J mice mainly because of resorptive changes in trabecular architecture.

Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures

Glucocorticoids are the most common cause of drug-related osteoporosis. We reviewed current evidence on risk factors for glucocorticoid-induced osteoporosis (GIOP) and prevention and treatment of GIOP-related fractures. Guidelines for GIOP management published since 2000 were also reviewed. Significant bone loss and increased fracture risk is seen with daily prednisone doses as low as 5 mg. Alternate-day glucocorticoid therapy can lead to similar bone loss. No conclusive evidence exists for a safe minimum dose or duration of glucocorticoid exposure. Physicians should consider risk factors for involutional osteoporosis such as older age, postmenopausal status, and baseline bone density measurements as they assess patients for prevention or treatment of GIOP. Bisphosphonates were reported to reduce GIOP-related vertebral fractures, but inconclusive data exist for hip fractures associated with glucocorticoid use. Hormone replacement therapy and parathyroid hormone analogs are effective in preserving bone density in GIOP. The risk of osteoporosis and fractures should be routinely assessed in patients receiving glucocorticoid therapy. Effective prevention and treatment options are available and can result in meaningful reduction of GIOP-related morbidity and mortality. Current guidelines for GIOP management recommend bisphosphonates, especially alendronate and risedronate, as first-line agents for GIOP, and these guidelines propose the preventive use of bisphosphonates early in the course of glucocorticoid therapy in high-risk patient subgroups.

Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands

Skeletal mass is maintained by a balance between cells which resorb bone (osteoclasts) and cells which form bone (osteoblasts). Bone development and growth is an on-going, life-long process. Bone is formed during embryonic life, grows rapidly through childhood, and peaks around 20 years of age (formation exceeds resorption). For humans the skeleton then enters a long period, approximately 40 years, when bone mass remains relatively stable. Skeletal turnover continues but the net effect of resorption and formation on bone mass is zero. For women this ends when they enter menopause and similar bone loss occurs for men, but later in life. These opposite functions are coupled, resorption precedes formation, and osteoblasts, or their precursors, stromal cells, regulate osteoclast formation and activity. Until recently, the molecular nature of this regulation, was poorly understood. However, recent observations have identified members of the TNF family of ligands and receptors as critical regulators of osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified. Its ligand, receptor activator of nuclear factor-κB ligand (RANKL), was quickly found, and shown to be expressed on stromal cells and osteoblasts. Its cognate receptor, RANK, was found to be expressed in high levels on osteoclast precursors. The interaction between RANKL and RANK was shown to be required for osteoclast formation. These observations have provided a molecular understanding of the coupling between osteoclastic bone resorption and osteoblastic bone formation. Moreover, they provide a framework on which to base a clear understanding of normal (e.g. postmenopausal osteoporosis and age associated bone loss) and pathologic skeletal changes (e.g. osteopetrosis, glucocorticoid-induced osteoporosis, periodontal disease, bone metastases, Paget's disease, hyperparathyroidism, and rheumatoid arthritis).

Possible involvement of vitamin D3-deficiency and relatively enhanced bone resorption in the development of bone loss in streptozotocin-induced diabetic rats

To explore the pathogenesis of diabetes associated osteopenia, we characterized the osteopenia in streptozotocin(STZ)-diabetic rats pharmacologically and biochemically. The femur metaphyseal bone mineral density measured by single photon absorptiometry decreased time-dependently in the STZ rats compared with that in control, and the difference reached statistical significance from 2 weeks after treatment with STZ. Closely similar bone loss was obtained in ovariectomized(Ovx) and vitamin D deficient(D(-)) rats. Daily oral treatment with a bone resorption inhibitor, FR78844(a bisphosphonate compound, 100 mg/kg), for 4 weeks significantly attenuated the osteopenia in the STZ and Ovx rats, but not in the D(-) rats, while 1α-hydroxyvitamin D3(1α-(OH)D3) significantly attenuated the osteopenia in the STZ and D(-) rats in a dose of 0.1 μg/kg/day, and that in the Ovx rats in 1 μg/kg/day. The latter dose of 1α-(OH)D3 significantly increased the metaphyseal bone mineral density of the femur in normal rats. Serum levels of 1α, 25-dihydroxyvitamin D(1α, 25-(OH)2D), the most active metabolite of vitamin D, hardly changed in the Ovx rats compared with that in control, but decreased to 24 and 76% that of control in the STZ and D(-) rats, respectively. Serum PTH levels in the STZ, Ovx and D(-) rats were comparable with those in control, but serum calcitonin levels were reduced to 60 and 66% of control in the STZ and Ovx rats, respectively. Serum osteocalcin levels also decreased in the STZ rats compared to control. It is thus speculated that the predominance of bone resorption over bone formation and the reduction of 1α, 25-(OH)2D are involved in the pathogenesis of diabetes associated osteopenia.

The mechanical control system of bone in weightless spaceflight and in aging

Bone loss is notable in elderly persons and in astronauts returning from spaceflight, however, the bone changes in these radically different patient populations appear morphologically similar. Bone structure depends upon several independent basic processes: growth, modeling, and remodeling. Each process follows a stereotyped sequence of steps. Alteration of any step may yield a similar bone loss, although from an entirely different mechanism. Mechanical forces appear to coordinate the fundamental bone shaping processes by a negative feedback control system. Determining how mechanical signals control the mass, architecture, and strength of bone may establish the limits by which exercise can prevent osteoporosis in the elderly and in astronauts despite obvious differences in etiology.