Severe magnesium deficiency compromises systemic bone mineral density and aggravates inflammatory bone resorption.

We sought to evaluate the effects of magnesium (Mg) intake deficiency on bone metabolism in rats with induced periodontal disease (PD). Holtzman rats were randomly divided into two groups: Control - animals fed a standard diet and test - animals fed a diet with 90% Mg deficiency. After 60 days on the diets, all animals received ligature on the lower left first molars to induce PD. Animals were euthanized after 30 days following ligature placement. Blood and urine were collected for determination of serum concentrations of Mg, calcium, osteocalcin (OCN), alkaline phosphatase and parathyroid hormone (PTH) by enzyme-linked immunosorbent assay, and the urinary concentration of deoxypyridinoline (DPD). Systemic bone mineral density (BMD), bone volume and architectural bone parameters were evaluated by micro-CT in L4 lumbar vertebrae and mandible. Tartrate-resistant acid phosphatase staining and immunohistochemical (IHC) analysis of inducible nitric oxide synthase (iNOS), Runt-related transcription factor 2 (RUNX2), CD86, CD80, proliferating cell nuclear antigen, vascular endothelial growth factor, OCN and osteopontin were investigated. Reverse-transcription polymerase chain reaction was employed to assess mRNA expression of receptor-activator of nuclear factor-kB ligand, osteoprotegerin (OPG) and interleukin (IL)-6. Mg deficiency was associated with higher concentrations of PTH and DPD, and significant decrease on both systemic and mandibular BMD, as well as greater severity of alveolar and trabecular bone loss. Significant increase in osteoclasts was observed in the test group with PD. IHC analysis showed significant increase in the expression of iNOS and decreased expression of OCN and RUNX2. Increased IL-6 mRNA and decreased OPG mRNA expressions were evidenced in the test group with PD. Mg deficiency caused systemic effects indicative of altered bone metabolism in the vertebrae and affected both immune and stromal cells, aggravating inflammatory bone resorption in the ligature-induced model of periodontitis.

Evaluation of bone turnover after bisphosphonate withdrawal and its influence on implant osseointegration: an in vivo study in rats.

OBJECTIVES: The aim of this study was to investigate bone turnover alterations after alendronate (ALD) withdrawal and its influence on dental implants osseointegration. MATERIALS AND METHODS: Seventy female Wistar rats were randomly divided in 2 groups that received on day 0 either placebo (control group-CTL; n = 10) or 1 mg/kg sodium alendronate (ALD; n = 60) once a week for 4 months. At day 120, ALD treatment was suspended for 50 animals. Then, a titanium implant was placed in the left tibia of each rat that were randomly allocated in five subgroups of ten animals each, according to the period of evaluation: day 0 (INT-0), day 7 (INT-7), day 14 (INT-14), day 28 (INT-28), and day 45 (INT-45) after ALD withdrawal. CTL group and a group that received ALD until the end of the experimental period (non-interrupted group-non-INT; n = 10) underwent implant placement on day 120. Animals were euthanized 28 days after implant surgery. Bone mineral density (BMD) of femur and lumbar vertebrae were evaluated by DXA, biochemical markers of bone turnover were analyzed by ELISA, and bone histomorphometry was performed to measure bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS: All groups receiving ALD showed higher BMD values when compared to CTL group, which were maintained after its withdrawal. Decreased concentrations in all bone turnover markers were observed in the non-INT group, and in the groups in which ALD was discontinued compared to the CTL group. The non-INT group showed lower %BIC and notably changes in bone quality, which was persistent after drug withdrawal. CONCLUSION: Collectively, the findings of this study demonstrated that ALD therapy decreased bone turnover and impaired bone quality and quantity around dental implants, and that its discontinuation did not reverse these findings. CLINICAL RELEVANCE: The severe suppression of bone turnover caused by the prolonged use of ALD may alter the capacity of bone tissue to integrate with the implant threads impairing the osseointegration process.

Assessment of CT numbers in limited and medium field-of-view scans taken using Accuitomo 170 and Veraviewepocs 3De cone-beam computed tomography scanners.

PURPOSE: To assess the influence of anatomic location on the relationship between computed tomography (CT) number and X-ray attenuation in limited and medium field-of-view (FOV) scans. MATERIALS AND METHODS: Tubes containing solutions with different concentrations of K2HPO4 were placed in the tooth sockets of a human head phantom. Cone-beam computed tomography (CBCT) scans were acquired, and CT numbers of the K2HPO4 solutions were measured. The relationship between CT number and K2HPO4 concentration was examined by linear regression analyses. Then, the variation in CT number according to anatomic location was examined. RESULTS: The relationship between K2HPO4 concentration and CT number was strongly linear. The slopes of the linear regressions for the limited FOVs were almost 2-fold lower than those for the medium FOVs. The absolute CT number differed between imaging protocols and anatomic locations. CONCLUSION: There is a strong linear relationship between X-ray attenuation and CT number. The specific imaging protocol and anatomic location of the object strongly influence this relationship.

Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: a novel ONJ mouse model.

Although osteonecrosis of the jaws (ONJ), a serious complication of antiresorptive medications, was reported a decade ago, the exact mechanisms of disease pathophysiology remain elusive. ONJ-like lesions can be induced in animals after antiresorptive treatment and experimental interventions such as tooth extraction or periapical or periodontal disease. However, experimental induction and manipulation of disease progression does not always reflect clinical reality. Interestingly, naturally occurring maxillofacial abscesses, inducing aggressive inflammation of the peri-radicular mucosa with significant osteolysis and alveolar bone expansion, have been reported in mice. Here, we aimed to explore whether osteonecrotic lesions would develop in areas of maxillary peri-radicular infections, in mice on antiresorptive medications with distinct pharmacologic action, thus establishing a novel ONJ animal model. Mice were treated with RANK-Fc or OPG-Fc that bind to RANKL or with the potent bisphosphonate zoledronic acid (ZA). Maxillae were assessed radiographically and histologically. µCT imaging of vehicle mice revealed several maxillae with altered alveolar bone morphology, significant ridge expansion and large lytic areas. However, in RANK-Fc, OPG-Fc and ZA treated animals the extent of bone loss was significantly less, but exuberant bone deposition was noted at the ridge periphery. BV and BV/TV were increased in the diseased site of antiresorptive vs. veh animals. Histologically, extensive inflammation, bone resorption and marginal gingival epithelium migration were seen in the diseased site of vehicle animals. Rank-Fc, OPG-Fc and ZA reduced alveolar bone loss, increased periosteal bone formation, and induced areas of osteonecrosis, and bone exposure that in many animals covered significant part of the alveolar bone. Collectively, our data demonstrate ONJ-like lesions at sites of maxillary peri-radicular infection, indistinguishable in mice treated with RAKL inhibitors vs. zoledronate. This novel mouse model of spontaneous ONJ supports a central role of osteoclast inhibition and infection/inflammation in ONJ pathogenesis and validates and complements existing animal models employing experimental interventions.

Influence of anatomical location on CT numbers in cone beam computed tomography.

OBJECTIVE: To assess the influence of anatomical location on computed tomography (CT) numbers in mid- and full field of view (FOV) cone beam computed tomography (CBCT) scans. STUDY DESIGN: Polypropylene tubes with varying concentrations of dipotassium hydrogen phosphate (K2HPO4) solutions (50-1200 mg/mL) were imaged within the incisor, premolar, and molar dental sockets of a human skull phantom. CBCT scans were acquired using the NewTom 3G and NewTom 5G units. The CT numbers of the K2HPO4 phantoms were measured, and the relationship between CT numbers and K2HPO4 concentration was examined. The measured CT numbers of the K2HPO4 phantoms were compared between anatomical sites. RESULTS: At all six anatomical locations, there was a strong linear relationship between CT numbers and K2HPO4 concentration (R(2)>0.93). However, the absolute CT numbers varied considerably with the anatomical location. CONCLUSION: The relationship between CT numbers and object density is not uniform through the dental arch on CBCT scans.