Bone Resorption

Treatment with anti-resorptive agents over 13 months was associated with for three to fivefold lower bone mineral density changes and 1.5-fold increased risk of incidence fracture in vitamin D insufficient as compared to vitamin D repleted postmenopausal osteoporotic women. Introduction Several drugs were registered for the treatment of osteoporosis on the basis of clinical trials in which vitamin D repletion was a pre-requisite inclusion criteria and vitamin D supplements were used as adjunctive therapy. However, in routine clinical practice these supplements are not consistently recommended. Methods We studied 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence > 75%. The patients were classified as vitamin D deficient (N=514) or vitamin D repleted (N=1001) according to risk factors (N=1062) or the level of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l (N=453). Results Vitamin D deficient and vitamin D repleted subjects differed significantly for annualized spine and hip bone mineral density (BMD) changes adjusted for all available confounding factors (type of treatment, age, global calcium intake, baseline BMD values). One hundred fifty one patients suffered from a new incident clinical fracture. The adjusted odds ratio for incident fractures in vitamin D deficient as compared to vitamin D repleted women was 1.77 (1.20 -2.59, 95% CI; p=0.004). Conclusions Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy.

The aim of this 10-year clinical trial was to evaluate the treatment outcome (condition of hard and soft peri-implant tissues, patient satisfaction, surgical and prosthetic aftercare) of mandibular overdentures supported by two or four implants. Materials and methods: Sixty edentulous patients with a mandibular height between 12 and 18 mm participated. Thirty patients were treated with an overdenture supported by two IMZ implants (group A) and 30 patients were treated with an overdenture supported by four IMZ implants (group B). Standardised clinical and radiographic parameters were evaluated 6 weeks after completion of the prosthetic treatment and after 1, 5 and 10 years of functional loading. Prosthetic and surgical aftercare was scored during the evaluation period, as well as patient satisfaction. Results: There were no statistically significant differences with regard to any of the studied clinical or radiographic parameters of the peri-implant tissues between the groups. In addition, no differences in satisfaction and aftercare were observed between the groups. Conclusion: There is no difference in the clinical and radiographical state of patients treated with an overdenture on two or four implants during a 10-year evaluation period. Patients of both groups were evenly satisfied with their overdentures and received the same amount of aftercare. For reasons of cost-effectiveness, a two-implant overdenture is advised for patients with a Cawood classes IV-VI resorption of the mandible and complaints concerning retention and stability of the lower denture.

The purpose of this investigation was to evaluate the extent to which obesity and/or hypertension may modify the response of rats' periodontium to chronic gingival irritation. Forty-four normal, spontaneously hypertensive, obese, and obese-hypertensive rats were used. Histopathologic evaluation of the periodontal structure showed both hyperplasia and hypertrophy of the walls of blood vessels supplying the periodontium in the hypertensive and obese-hypertensive animals. The results also indicated that obesity significantly contributed to e severity of periodontal disease. Hypertension alone was not a significant factor. The obese-hypertensive rats showed the most severe periodontal response to local irritation.

Plaque-induced lesions can produce peri-implant bone loss with ultimate implant loss. Although the peri-implant tissues seem to be more resistant than the periodontal ones to plaque and calculus, they can produce a more extensive spread of the infection to the deeper tissues around implants. The case of a 45year-old female patient is presented in which, over a three year period, there was a progressive loss of peri-implant bone and the formation of a periapical radiolucency with an external fistula. The implant was removed and examined with the cutting-grinding system. Microscopy examination showed that most of the hydroxyapatite (HA) was still adherent to the metal. There was a detachment in the area of the HA-titanium interface. The implant surface was almost completely covered by bacteria. Bacteria were also present in the bone medullary spaces surrounding the implant. The infection of the periodontal tissues had progressed into the alveolar bone, thus producing a localized bone infection. The cause of the implant failure is probably related to a defective connection of the abutment or to overloading of the implant due to the presence of interlocks in the prosthetic restoration.

Bone remodeling due to stress-shielding has been studied using a model system consisting of metal-polymer laminated fixation plates securely fixed to canine femurs. The plate stiffness was controlled by varying the ratio of metal facing to polymer core thickness in the laminate design while secure fixation to bone was achieved by providing a porous bone interfacing surface for the ingrowth of bone from the periosteal sur-face. Observations of laterally and medially placed plates indicated resorption in the area of the periosteal and endosteal bone surfaces respectively, for the higher stiffness composite plates used. The results indicate that plate stiffness greater than approximately 70 GPa (axial) and 6 N m2 (flexural) will result in extensive bone remodeling in the canine femur after a six month implantation period.

Alteration in biochemical markers of bone turnover and bone mineral density (BMD) of whole body and isolated femur and tibia in relation to age, estrous cycle, pregnancy and lactation and suitability of use of rat as model for studies on pathophysiology of bone and therapeutic measures for its management were investigated. Immature rats (1, 1.5 and 2 month of age; weighing, respectively, 39.3 ± 1.0, 67.8 ± 2.4 and 87.2 ± 5.2 g) exhibited high rate of bone turnover, as evidenced by high serum osteocalcin and alkaline phosphatase and urine calcium/creatinine ratio. However, their BMD (whole body or of isolated long bones) was below measurable levels. Marked increase in body weight at 3 months (185.5 ± 5.2 g) was associated with low serum osteocalcin and alkaline phosphatase and urine calcium/creatinine ratio. Biochemical markers and BMD attained at puberty at 3 months were maintained until 36 month of age. No significant change in serum calcium was observed with increasing age or on any of the biomarkers during estrous cycle, and BMD of femur and tibia isolated during proestrus and diestrus stages was almost similar. Onset of pregnancy was associated with significant increase in serum total alkaline phosphatase and osteocalcin levels, but serum calcium, urine calcium/creatinine ratio or BMD of whole body or isolated long bones were not significantly different from that at proestrus stage. No marked change, except increase in body weight (P < 0.05), was also evident in these parameters between days 5 and 19 of pregnancy, irrespective of number of implantations in the uterus. A significant decrease in BMD of isolated femur (neck and mid-shaft regions) was observed on days 5 and 21 of lactation as compared to that during pregnancy or diestrus/proestrus stages of estrous cycle; the decrease being almost similar in females lactating two or six young ones. BMD of isolated tibia (global and region proximal to tibio-fibular separation point), though generally lower than that during cycle and pregnancy, was statistically non-significant. However, clear evidence of occurrence of osteoporosis during lactation, with decrease in BMD of >2.5 × S.D. in isolated femur (global, neck and mid-shaft) as well as tibia (global) was observed only when BMD data was analysed on T-/Z-score basis. Serum biochemical markers of bone turnover, too, were significantly increased in comparison to cyclic rats. Findings demonstrate marked increase in body weight and bone turnover during first 3 months of age, direct correlation between peak bone mass and onset of puberty at 3 months of age and increase in bone resorption rate during lactation. Finding of the study while might suggests possible use of rat as useful model for studies on bone turnover rate during lactation and post-weaning periods and extrapolation of the result to the human situation, but not in relation to ageing.

The effects of Spinal Cord Injury (SCI) on bone in paralyzed areas are well documented but there are few data for the importance of the level of injury in the decrease of mechanical strength in paralyzed legs. The aim of the present study was to describe bone loss of the separate compartments of trabecular and cortical bone in spinal cord injured men and to compare possible changes in mechanical properties of tibia with the neurological level of injury. Fifty men were included in this study: 39 had complete SCI in chronic stage. As chronic stage, we considered paraplegia &gt;1.5 years (yrs). Men were separated as follows: Group A (18 men, high paraplegia: Thoracic (T)4-T7 level, mean age: 33 yrs, duration of paralysis: 5.9 yrs) and group B (21 men, low paraplegia: T8-T12 level, mean age: 39 yrs, duration of paralysis: 5.6 yrs) in comparison with 11 healthy men as a control group (C) of similar age, height, and weight. None of the subjects was given bone acting drugs. The neurologica...

Mounting evidence exists for the operation of a functional serotonin (5-HT) system in osteoclasts and osteoblasts, which involves both receptor activation and 5-HT reuptake. In previous work we showed that the serotonin transporter (5-HTT) is expressed in osteoclasts and that its activity is required by for osteoclast differentiation in vitro. The purpose of the current study was to determine the effect of treatment with fluoxetine, a specific serotonin reuptake inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in femurs and vertebrae as determined by micro-computed tomography (mCT). This correlated with an increase in trabecular number, connectivity, and decreased trabecular spacing. Fluoxetine treatment also resulted in increased volume in vertebral trabecular bone. However, fluoxetine-treated mice were not protected against bone loss after ovariectomy, suggesting that its anabolic effect requires the presence of estrogen. The effect of blocking the 5-HTT on bone loss following an LPS-mediated inflammatory challenge was also investigated. Subcutaneous injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in increased numbers of osteoclasts and net bone loss, whereas new bone formation and a net gain in bone mass was seen when LPS was given together with fluoxetine. We conclude that fluoxetine treatment in vivo leads to increased bone mass under normal physiologic or inflammatory conditions, but does not prevent bone loss associated with estrogen deficiency. These data suggest that commonly used anti-depressive agents may affect bone mass.

Osteoporosis is a common complication in cystic fibrosis (CF) patients. In this study, we performed a histomorphometric analysis of the bones of a mouse genetic model of human CF in which both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are inactivated. We find that, even in the absence of obvious nutritional and therapeutic differences, the CFTR mutation is associated with severe osteopenia. Bone mineral density (BMD) of total body and of individual bones is significantly diminished. CFTR mutants display a striking significant (50%) reduction of cortical bone width and thinner trabeculae. Analysis of dynamic parameters indicates a significant reduction of bone formation and a concomitant strong increase in bone resorption. Active osteoclasts where found mostly associated with cortical bone. Our data support the concept that CF-associated osteoporosis is part of the syndromic symptoms associated with the CFTR mutation.

Osteoclasts are multinucleated cells of hematopoietic origin which are unique in their ability to resorb bone. Osteoclasts are generated from myeloid progenitors through a progression that involves the fusion of mononuclear precursor cells. The identification of RANK-RANKL signaling as the main signal regulating osteoclast differentiation was a major breakthrough in the bone biology field. In addition remarkable discoveries have been made to broaden the knowledge of the molecular mechanisms of osteoclast formation and differentiation. Despite the vital requirement of osteoclasts in bone modeling and remodeling, bone-related conditions like osteoporosis, Paget&#39;s disease and rheumatoid arthritis where accelerated bone resorption takes place pose a major socioeconomic burden to the society. Hence, a better understanding of the pathways leading to osteoclast differentiation is vital in successfully managing such diseases. This is an attempt to give a birds-eye-view of the players in...

The aim of this study was to compare changes in periodontal status of a Swedish population over a 10-year period expressed as frequency distributions of individuals according to severity of periodontal disease experience. The study involved 600 randomly selected individuals evenly distributed into age groups 20, 30, 40, 50, 60 and 70 years, examined in 1973 and another randomly selected group of 597 individuals similarly age distributed and examined in 1983. Based on clinical data and full mouth intraora! radiographs all individuals were classified into 5 groups according to severity of periodontal disease experience. In 1983, 23% of the individuals were classified as having healthy periodontal tissues, group 1, compared to 8% in 1973. The changes were most pronounced in the age groups 20 and 30 years, among whom 58% and 35%, respectively, were registered as having healthy periodontium in 1983, The prevalence of individuals with gingivitis without signs of lowered periodonta! bone level, group 2, was 22% in 1983 compared to 41% in 1973. in all, 49% ofthe dentate population in 1973 and 45% in 1983 showed no marginal alveolar bone loss. Moderate peridonta! bone loss, group 3, was found in 41% ofthe population in 1983 compared to 47% in 1973, Among 30-. 40-, and 50-year-olds, there were more, and among 60-and 70-yearolds, fewer individuals in this group in 1983 compared to 1973, 96% ofthe dentate population were classified as belonging to groups 1, 2 or 3 in 1973 compared to 86% in 1983. Individuals with severe periodontal bone ioss, group 4, were few in 1973 and not found before the age of 50, In 1983, the prevalence of individuals belonging to group 4 had increased and amounted to 1% ofthe 20year-olds, 9% of the 50-year-olds, 25% of 60-year-olds and 38%i of 70-year-olds. On the average, 11% of the dentate population were found in group 4 in 1983 compared to 2% in 1973. The prevalence of individuals belonging to group 5, i.e., alveolar bone loss around the majority ofthe teeth exceeding Vj ofthe normal bone height and the presence of angular bony defects and/or furcation defects, was 1% in 1973 and 2% in 1983. There were no individuals younger than 40 years in this group. Based on gingivitis and probing pocket scores, 33% of the individuals classified to groups 3 and 4 were considered periodontaliy healthy although with reduced periodontal support. In periodontal disease severity group 5, no individual was considered periodontaliy healthy.

Disuse induces rapid and severe bone loss in larger mammals as a result of greatly elevated osteoclastic resorption. In this study, we tested whether risedronate (RIS), a potent inhibitor of osteoclastic activity, would effectively prevent cancellous bone loss in female beagles (5 -7 years old, N = 28) subjected to single forelimb immobilization (IM) for 12 months. Age-matched, non-IM dogs served as controls (Con). Half the animals from each group received RIS 1 mg/kg p.o. daily (Con + RIS, IM + RIS). Remaining dogs received sterile water (Con, IM). Histomorphometry showed that IM caused a dramatic reduction in cancellous bone mass (À71%) of distal 2nd metacarpals, characterized by marked decreases in trabecular width (À51%) and number (À41%), and 4-fold increases in the indices of bone resorption (eroded surface, osteoclast number, and surface). Bone formation indices (calcein-labeled surface, osteoid surface, and bone formation rate) were also significantly higher in IM than in controls. Activation frequency in IM increased about 4-fold beyond control level. RIS treatment reduced, but did not abolish cancellous bone loss due to immobilization. IM animals treated with RIS lost nearly 50% of cancellous bone mass, while trabecular width and number were reduced by 31% and 25%, respectively. In both RIS-treated control and IM animals, overall bone formation parameters (mineralized bone surface fraction and bone formation rate) remained roughly at intact control levels; however, mineral apposition rate relative to intact control was reduced 40% in RIS-treated control and 86% in RIS-treated IM animals. These results indicate that high-dose RIS treatment might suppress osteoblastic function, especially under long-term disuse. Interestingly, bone resorption parameters in RIS-treated IM animals reached levels even higher than in vehicle-treated IM animals; values for eroded surface, osteoclast number, and surface were 84%, 53%, and 83% above vehicle-treated IM values, respectively. Our data indicate that risedronate treatment is partially effective in preventing cancellous bone loss during long-term disuse. Moreover, our results suggest that bisphosphonates can impair the ability of mature osteoclasts to resorb bone, but cannot overcome the strong stimulus for osteoclast recruitment caused by long-term disuse. D

Feline osteoclastic resorptive lesions (FORL) of the teeth are common in cats, and lead to pain, destruction of the periodontal ligament, and tooth loss. The expression of interleukin (IL)-1β and IL-6 mRNA was higher in teeth with FORL than in normal teeth (P<0·01 and P<0·001, respectively), but no such differences were found between pathological and normal gingival tissue samples. There were no differences between teeth affected with FORL and normal teeth in respect of the expression of receptor activator of NFκB ligand (RANKL) mRNA or osteoprotegerin (OPG) mRNA. However, OPG mRNA expression was higher in gingival tissue associated with teeth affected with FORL than in normal gingival tissue (P<0·05), whereas the reverse was true of RANKL mRNA expression (P<0·05). OPG mRNA expression was significantly higher in teeth than in femoral and alveolar bone (P<0·001). RANKL and OPG mRNAs were detected in all tissues examined. The data suggest that the elevated expression of IL-lβ and IL-6 mRNA plays a role in the mediation of osteoclast activity in advanced FORL. In contrast, OPG and RANKL do not appear to regulate osteoclasts in advanced disease. The results also suggest that OPG and RANKL mRNA play a role in mediating inflammatory responses in gingival cells, and that OPG has an inhibiting effect on tooth resorption.

The suitability of a mouse model for host response in the induction of alveolar bone loss by Porphyromonas gingiualis was explored. The mouths of immunocompetent and severe combined immunodeficient (SCID) mice were infected with P. gingivalis ATCC 53977. P. gingiualis was not isolated from the mouths of these mice before infection, but was present at least 42 days after infection. P.

The purposes of the present study were to evaluate the effects of frequent applications of low-level laser therapy (LLLT) on corticotomy-assisted tooth movement in a beagle dog model and to compare the effects in the mandible and maxilla. Materials and Methods: In 4 male beagles, the maxillary and mandibular second premolars were extracted. The third premolars were corticotomized and then protracted from the canines with a continuous force of 200 g. Daily LLLT (using an aluminum gallium indium phosphide [AlGaInP] diode) was applied at the buccal mucosa of the corticotomized premolars on 1 side only. The tooth movement was measured for 8 weeks. Fluorochromes were injected intravenously at the start of the experiment (T0) and after 2 (T2), 4 (T4), and 8 (T8) weeks to evaluate new bone formation on the tension sides. Histomorphometric and immunohistologic evaluations were performed. Results: In the mandible, the movement of the corticotomized premolars in the LLLT plus corticotomy group was less than that in the corticotomy-only group, although the difference was not statistically significant. In the maxilla, no significant differences between the 2 groups were found. Osteoclastic and proliferating cell activities and the amount of new bone formation were greater in the mandibular LLLT plus corticotomy group than in the corticotomy-only group. Conclusions: The frequent application of LLLT showed no significant effect on the corticotomized tooth movement.

To elucidate the histological events that follow administration of eldecalcitol, a second-generation of vitamin D analog currently awaiting approval as a drug for treatment of osteoporosis, we employed the ovariectomy (OVX) rat model. OVX rats received vehicle or 30 ng/kg of eldecalcitol, and sham-operated animals received vehicle only. Rats were sacrificed after 12 weeks and had their femora and tibiae removed and processed for histochemical and histomorphometrical analyses. When compared with OVX group, osteoclastic number and bone resorption parameters were significantly reduced in eldecalcitol-treated rats, accompanied by decreased bone formation parameters. The preosteoblastic layer, with which osteoclastic precursors interact for mutual differentiation, was poorly developed in the eldecalcitol group, indicating less cell-to-cell contact between preosteoblasts and osteoclast precursors. Interestingly, eldecalcitol did promote a type of focal bone formation that is independent of bone resorption, a process known as bone minimodeling. While the number of ED-1positive macrophages was higher in the bone marrow of treated rats, though osteoclastic number was deceased. Taken together, our findings suggest that eldecalcitol stimulates preosteoblastic differentiation rather than their proliferation, which in turn may prevent or diminish cell-to-cell contact between preosteoblasts and osteoclastic precursors, and therefore, lead to lower osteoclast numbers and decreased bone resorption.

The function of osteoclasts is to digest the calcified bone matrix. Osteoclasts, together with myotubes, are among the rare examples of multinucleated cells found in higher vertebrates, resulting from the fusion of mononucleated progenitors belonging to the monocyte/macrophage lineage. So far, no information is available about function and transcriptional activity of multiple nuclei in osteoclasts. We have used a run-on technique to visualize RNA synthesis in individual nucleus. We provide the first evidence that nuclei of resorbing osteoclasts, isolated from chick embryo long bones, or differentiated in vitro from murine spleen cells in presence of RANKL and macrophage-colony stimulating factor, are all transcriptionally active. Nevertheless, if transcriptional activity is the same for all the nuclei within a cell, its level varies between osteoclasts: osteoclasts with highly active nuclei are always associated with resorption pits. We found that global transcription activity of resorbing osteoclasts seeded on calcified matrix is down-regulated after 5-h treatment with calcitonin, which transiently blocks resorption. This effect is reversible because calcitonin removal led to nuclear transcription activation. These results indicate a strong correlation between transcription and resorption. Finally, our data indicate that the resorption pit surface is linearly related to the nuclei number per osteoclast, strongly suggesting that functional advantage of osteoclast multinucleation is to improve resorption efficiency. Abbreviations: BrU, Bromouridine; BrUTP, 5Ј bromouridine triphosphate; LSM, leukocyte separation medium; M-CSF, macrophage-colony stimulating factor; TRAP, tartrate-resistant acidic phosphatase; TBS, Tris-buffered saline.

Individuals often perform exercise in the fasted state, but the effects on bone metabolism are not currently known. We compared the effect of an overnight fast with feeding a mixed meal on the bone metabolic response to treadmill running. Ten, physically-active males aged 28 ± 4 y (mean ± 1SD) completed two, counterbalanced, 8 d trials. After 3 d on a standardised diet, participants performed 60 min of treadmill running at 65% V02max on Day 4 following an overnight fast (FAST) or a standardised breakfast (FED). Blood samples were collected at baseline, before and during exercise, for 3h after exercise, and on four consecutive follow-up days (FU1-FU4). Plasma/serum were analysed for the c-terminal telopeptide region of collagen type 1 (P-CTX), n-terminal propeptides of procollagen type 1 (P1NP), osteocalcin (OC), bone alkaline phosphatase (bone ALP), parathyroid hormone (PTH), albumin-adjusted calcium, phosphate, osteoprotegerin (OPG), Cortisol, leptin and ghrelin. Only the P-CTX response was significantly affected by feeding. Pre-exercise concentrations decreased more in FED compared with FAST (47% vs 26%, P < 0.001) but increased during exercise in both groups and were not significantly different from baseline at 1 h post-exercise. At 3 h post-exercise, concentrations were decreased (33%, P < 0.001) from baseline in FAST and significantly lower (P < 0.001) than in FED. P1NP and PTH increased, and OC decreased during exercise. Bone markers were not significantly different from baseline on FU1-FU4. Fasting had only a minor effect on the bone metabolic response to subsequent acute, endurance exercise, reducing the duration of the increase in P-CTX during early recovery, but having no effect on changes in bone formation markers. The reduced duration of the P-CTX response with fasting was not fully explained by changes in PTH, OPQ leptin or ghrelin.

The ability of extremely low-amplitude mechanical strains to promote bony ingrowth was evaluated in an in vivo animal model, the functionally isolated turkey ulna. A cylindrical, porous-coated titanium implant was placed across the dorsal and ventral cortices of the left ulna diaphysis of 12 animals. Back scatter electron microscopy was used to quantify the relative bony ingrowth after eight weeks of: ( I ) disuse alone, (2) disuse plus 100 seconds per day of a 1-Hz, 150-microstrain (pt) mechanical stimulus, or (3) disuse plus 100 seconds per day of a 20-Hz stimulus of similar strain magnitude. Disuse alone caused a mean 8.3% (-+5.5%) loss of bone away from the implant, with the area between implant and bone actively filling with a fibrous membrane. A daily 100-second regimen of low-magnitude, 1-Hz mechanical stimulation caused 28% (26.2%) of the implant area available for ingrowth to be filled with bone. At 20 Hz, the amount of bony ingrowth increased to 69% (23.0%). These data demonstrate that brief exposure to extremely low-amplitude mechanical strains can enhance the biologic fixation of cementless implants. Moreover, the degree of ingrowth is dependent on the frequency of the applied strain.

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks-pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)-showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH) 2 D 3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre-(P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH) 2 D 3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH) 2 D 3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH) 2 D 3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis.

The objective of this study was to determine the effect of calcium phosphate mineral content on the bone in-growth at the expense of composite of co-polylactide polymer charged with 2 different ratios of b-TCP granules (10 and 24 w-% of b-TCP). The evaluation was realized in a long term rabbit bone model. After 24, 48 and 76 weeks, the implants were examined by micro CT, scanning electron microscopy (SEM) using backscattered electron (BSE) and light microscopy (polarized and blue light microscopy). No foreign body reaction was detected during the 76 weeks follow-up in any of the test samples. Polymer hydrolysis began at approximately 24 weeks, by 76 weeks, the pure polymer implant had begun to release P(96L/4D)LA particles and show signs of peripheral localized bone resorption. A decrease in the amount of CaP was noticed between 24 and 76 weeks in both 10 wt-% and 24 wt-% b-TCP/P(96L/4D)LA composites. The study showed that the highest bone in-growth was with 24 wt-% b-TCP/P(96L/4D)LA composite. Bone in-growth and mineralization were evident for the composites associated with specific peripheral bone architecture. Fluorescent labelling demonstrated high bone in-growth and remodeling at the interface, while for pure co-polymer no bone remodeling or bone activity was maintained after 48 weeks. The study demonstrated the positive effect of calcium phosphate content into P(96L/4D)LA. This kind of composite is a suitable resorbable osteoconductive matrix, which provides long term stability required for ligament fixation device.

Given that the unerupted tooth is encased in alveolar bone, an understanding of the biology of bone resorption to form an eruption pathway is a central theme in tooth eruption. To that end, Cahill (1969) dissociated tooth movement from eruption pathway formation by placing transmandibular wires over dog premolars prior to the onset of eruption. An eruption pathway formed in the alveolar bone above the temporarily impacted premolars, and when the wires were removed, the tooth rapidly erupted. In succedaneous dentition, this pathway follows the gubernacular canal above each tooth; i.e., bone resorption widens this canal to allow the crown to move through it and exit the alveolar bone . Thus, there is a template (gubernacular canal) for the eruption pathway, and, at a given time, bone resorption by osteoclasts will ABSTRACT: Tooth eruption is a complex and tightly regulated process that involves cells of the tooth organ and the surrounding alveolus. Mononuclear cells (osteoclast precursors) must be recruited into the dental follicle prior to the onset of eruption. These cells, in turn, fuse to form osteoclasts that resorb alveolar bone, forming an eruption pathway for the tooth to exit its bony crypt. Some of the molecules possibly involved in the signaling cascades of eruption have been proposed in studies from null mice, osteopetrotic rodents, injections of putative eruption molecules, and cultured dental follicle cells. In particular, recruitment of the mononuclear cells to the follicle may require colony-stimulating factor-one (CSF-1) and/or monocyte chemotactic protein-1 (MCP-1). Osteoclastogenesis is needed for the bone resorption and may involve inhibition of osteoprotegerin transcription and synthesis in the follicle, as well as enhancement of receptor activator of NFB ligand (RANKL), in the adjacent alveolar bone and/or in the follicle. Paracrine signaling by parathyroid-hormone-related protein and interleukin -1␣, produced in the stellate reticulum adjacent to the follicle, may also play a role in regulating eruption. Osteoblasts might also influence the process of eruption, the most important physiologic role likely being at the eruptive site, in the formation of osteoclasts through signaling via the RANKL/OPG pathway. Evidence thus far supports a role for an osteoblast-specific transcription factor, Cbfa1 (Runx2), in molecular events that regulate tooth eruption. Cbfa1 is also expressed at high levels by the dental follicle cells. This review concludes with a discussion of the several human conditions that result in a failure of or delay in tooth eruption.

The purpose of this study was to evaluate the outcome of trabecular metal (TM) acetabular components used in revision hip arthroplasty with major bone deficiency. We retrospectively reviewed the records of 46 patients undergoing revision hip arthroplasty with severe acetabular bone loss. Clinical outcomes were assessed using Harris Hip Score, Western Ontario and McMaster Universities, and Short-Form 12. Mean follow-up was 50 months. All patients had Paprosky type IIc or III acetabular bone deficiency. Major complications included 1 infection, 2 dislocations, and 1 arterial bleeding. Average Harris Hip Score was 78.2. Short-Form 12 scores were within population-based age-matched averages. Western Ontario and McMaster Universities scores were mainly in the 2 lowest disability categories. Porous tantalum shows promising results in revision arthroplasty with severe acetabular bone loss.

To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults. Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P &lt; .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P &lt; .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently recei...

Objective: We compared the effect of supplementation with a fortified skimmed milk product (high calcium skim milk) with or without added phylloquinone (vitamin K 1 ) on markers of bone formation and resorption in premenopausal women. Methods: Eighty-two women 20 to 35 y of age were randomly allocated to three groups. Two groups received two daily servings of high calcium skim milk (1000 mg/d of extra calcium) with or without added phylloquinone (80 g/d) for 16 wk, and a third control group received no supplementation. Bone density was assessed at baseline and the bone markers, total osteocalcin, type I N-terminal procollagen peptide, and cross-linked C-telopeptide of type I collagen were measured at baseline and at weeks 2, 12, and 16. Serum phylloquinone and undercarboxylated osteocalcin were measured in the control and vitamin K-supplemented groups at weeks 0 and 16. Results: Baseline values for age, body mass index, and bone density did not differ across groups. In vitamin K-supplemented women, mean serum phylloquinone concentrations increased from 0.27 to 0.76 g/L (P Ͻ 0.05) and undercarboxylated osteocalcin concentrations decreased from 9.68 to 4.46 g/L (P Ͻ 0.05) over 16 wk. Plasma cross-linked C-telopeptide of type I collagen, total osteocalcin, and type I N-terminal procollagen peptide levels decreased significantly in both supplemented groups compared with the control group over 16 wk (cross-linked C-telopeptide of type I collagen Ͼ30%, total osteocalcin and type I N-terminal procollagen peptide Ͼ15%). Conclusion: Fortified milk supplementation in premenopausal women reduced bone turnover significantly. Phylloquinone fortification substantially improved vitamin K status but had no demonstrable additive effect on bone turnover in this short-term study.

Purpose: To determine whether low-dose creatine and protein supplementation during resistance training (RT; 3 dIwk j1 ; 10 wk) in older men (59-77 yr) is effective for improving strength and muscle mass without producing potentially cytotoxic metabolites (formaldehyde). Methods: Older men were randomized (double-blind) to receive 0.1 gIkg j1 creatine + 0.3 gIkg j1 protein (CP; n = 10), creatine (C; n = 13), or placebo (PLA; n = 12) on training days. Measurements before and after RT included lean tissue mass (air-displacement plethysmography), muscle thickness (ultrasound) of elbow, knee, and ankle flexors and extensors, leg and bench press strength, and urinary indicators of cytotoxicity (formaldehyde), myofibrillar protein degradation [3-methylhistidine (3-MH)], and bone resorption [cross-linked N-telopeptides of type I collagen (NTx)]. Results: Subjects in C and CP groups combined experienced greater increases in body mass and total muscle thickness than PLA (P G 0.05). Subjects who received CP increased lean tissue mass (+5.6%) more than C (+2.2%) or PLA (+1.0%; P G 0.05) and increased bench press strength (+25%) to a greater extent than C and PLA combined (+12.5%; P G 0.05). CP and C did not differ from PLA for changes in formaldehyde production (+24% each). Subjects receiving creatine (C and CP) experienced a decrease in 3-MH by 40% compared with an increase of 29% for PLA (P G 0.05) and a reduction in NTx (j27%) versus PLA (+13%; P = 0.05). Conclusions: Low-dose creatine combined with protein supplementation increases lean tissue mass and results in a greater relative increase in bench press but not leg press strength. Lowdose creatine reduces muscle protein degradation and bone resorption without increasing formaldehyde production.

A follow-up of disc herniation (herniated nucleus pulposus [HNP]) resorption on magnetic resonance imaging (MRI). To assess the determinants of resorption of HNP. Neovascularization in the outermost areas of HNP, presenting as an enhancing rim in gadolinium diethylenetriamine pentaacetic acid MR images, is thought to be a major determinant of spontaneous resorption of HNP. Patients with HNP-induced sciatica at baseline were rescanned at 2 months (N = 74) and after 12 months (N = 53). The volume of HNP (mm), thickness (mm) and extent (%) of enhancement, and the degree of HNP migration (Komori classification) were analyzed. Repeated measures analysis of covariance was used in statistical analysis. Significant resorption of HNP occurred from baseline to 2 months, although the resorption rate was more pronounced over the whole 1-year follow-up. Higher baseline scores of rim enhancement thickness, higher degree of HNP displacement in the Komori classification, and age category 41-50 year...

This prospective clinical study evaluated the 5-year survival and success rates of 66 titanium implants placed in bone that had been previously augmented with autografts and nonresorbable barrier membranes. During the observation period, three patients with five implants dropped out of the study. None of the remaining 61 implants were lost during the follow-up period (implant survival rate of 100%). One implant exhibited a periimplant infection, whereas 60 implants were considered clinically successful at the 5-year examination, resulting in a 5-year success rate of 98.3%. It can be concluded that the clinical results of implants in regenerated bone are comparable to those of implants in nonregenerated bone. (Int J Periodontics

ÐIn testing for the cytotoxicity of medical devices, crucial parameters are the type of cells, the duration of the exposure, the physical form of the device and the method of evaluation. Using cell cultures the changes of cell functions induced by arti®cial materials may be evaluated. In screening tests the eect of biomaterials on functions common to all cell types is investigated through both continuous lines and primary cultures. In supplementary tests the eect of biomaterials on speci®c functions is studied, employing cells of the same type of those which will be in contact with the device in vivo. Osteoblasts, either from primary culture or an established line, are used to study the interaction with materials for bone implants. We evaluated whether dental cements aect the replication cycle of osteoblast-like cells MG63. The S phase was inhibited by the cements with a phenolic group, even though to a dierent extent. Mononuclear cell cultures are used to investigate the immune response, which is important in the host reaction to implant. We investigated whether the chromium ions released in a bio-logical¯uid may induce PBMC to produce cytokines involved in bone resorption. Chromium extract did not impair TNFa release signi®cantly, but inhibited IL-6 release signi®cantly in stimulated PBMC. Endothelial cell cultures are useful to the evaluation of materials for vascular grafts. We studied the inuence of some types of Dacron on endothelial functions. Collagen-coated Dacron decreased signi®cantly the production of 6-keto-prostaglandin F 1a. Knitted Dacron caused a signi®cant increase of tissue factor, a signi®cant reduction in PECAM-1 and a signi®cant increase in ELAM-1.

The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDLrelated receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action. ß predominantly of cancellous bone such as the femoral neck. (4) Moreover, greater cortical bone mass may explain the higher resistance to vertebral fracture in males compared to females. Despite the influence of cortical bone and specifically the periosteum on fracture prevention, the mechanisms that govern cortical bone biology and the response of this site to osteoporotic therapies are far from being understood.