β2-Adrenoceptor Deficiency Results in Increased Calcified Cartilage Thickness and Subchondral Bone Remodeling in Murine Experimental Osteoarthritis

PurposeRecent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of knee OA in β2-AR-deficient (Adrb2-/-) mice after surgical OA induction.MethodsOA was induced by destabilization of the medial meniscus (DMM) in male wildtype (WT) and Adrb2-/- mice. Cartilage degeneration and synovial inflammation were evaluated by histological scoring. Subchondral bone remodeling was analyzed using micro-CT. Osteoblast (alkaline phosphatase - ALP) and osteoclast (cathepsin K - CatK) activity were analyzed by immunostainings. To evaluate β2-AR deficiency-associated effects, body weight, sympathetic tone (splenic norepinephrine (NE) via HPLC) and serum leptin levels (ELISA) were determined. Expression of the second major AR, the α2-AR, was analyzed in joint tissues by immunostaining.ResultsWT and Adrb2-/- DMM mice developed comparable changes in cartilage degeneration and synovial inflammation. Adrb2-/- DMM mice displayed elevated calcified cartilage and subchondral bone plate thickness as well as increased epiphyseal BV/TV compared to WTs, while there were no significant differences in Sham animals. In the subchondral bone of Adrb2-/- mice, osteoblasts activity increased and osteoclast activity deceased. Adrb2-/- mice had significantly higher body weight and fat mass compared to WT mice. Serum leptin levels increased in Adrb2-/- DMM compared to WT DMM without any difference between the respective Shams. There was no difference in the development of meniscal ossicles and osteophytes or in the subarticular trabecular microstructure between Adrb2-/- and WT DMM as well as Adrb2-/- and WT Sham mice. Number of α2-AR-positive cells was lower in Adrb2-/- than in WT mice in all analyzed tissues and decreased in both Adrb2-/- and WT over time.ConclusionWe propose that the increased bone mass in Adrb2-/- DMM mice was not only due to β2-AR deficiency but to a synergistic effect of OA and elevated leptin concentrations. Taken together, β2-AR plays a major role in OA-related subchondral bone remodeling and is thus an attractive target for the exploration of novel therapeutic avenues.

Five-Year Prospective Study on Implant Failure and Marginal Bone Remodeling Expected Using Bone Level Implants with Sandblasted/Acid-Etched Surface and Conical Connection

Objective The purpose of the present prospective, case-series study was to report implant survival rate and marginal bone remodeling expected 5 years after loading using dental implants placed in daily practice. Materials and Methods This research was designed as an open-cohort, prospective, case-series evaluation. Any partially or completely edentulous patient, scheduled to receive at least one bone level implant, was considered eligible for this study. Primary outcome measurements were: implant and prosthetic cumulative survival rate and any complications experienced up to the 5-year follow-up. Secondary outcome measures were: thickness of gingival biotype, implant insertion torque, implant stability quotient, and marginal bone loss (MBL). Results Ninety consecutive patients (34 males and 56 females, aged between 24 and 81 years old [mean: 53.2 ± 15.4]) with 243 inserted implants were followed for at least 5 years after loading (mean: 65.4 ± 3.1 months; range from 60 to 72). At the 1-year follow-up, no drop-outs were recorded, but 17 patients (18.9%) with 18 restorations (12.6%) delivered on 34 implants (14%) were lost at the 5-year examination. At the 5-year follow-up examination, six implants lost osseointegration (97.5%). In the same period, four prostheses failed (97.2%). Five complications were reported in five different patients (prosthetic success rate was 96.5%, at patient level). Five years after loading, the mean MBL was 0.41 ± 0.30 mm. The difference from the 1-year data was 0.04 ± 0.19 mm. A statistically significant higher MBL was found for smokers, and patients with thin gingival biotype. The mean implant insertion torque was 42.9 ± 4.8 Ncm (range from 15 to 45 Ncm). Two-hundred and three implants (83.5%) were inserted with an insertion torque ≥35 and ≤45 Ncm. Conclusions High implant survival and success rate could be expected with stable marginal bone remodeling up to 5 years after loading. Smoking and thin tissue biotype were the most important variabilities associated with higher MBL. Further research studies are needed to confirm these results.

Ethnic characteristics of bone remodeling in female patients with type 2 diabetes mellitus

Background: Structural and metabolic disorders of bone tissue in women with T2DM have no clinical manifestations, but they are accompanied by the risk of fractures.Aim: To study the parameters of bone metabolism, BMD and microarchitectonics in female patients with T2DM in the Buryat population.Materials and methods: The observational single-center one-stage controlled study included 73 women with T2DM, which were divided into 2 groups depending on the functional state of the ovaries (reproductive and postmenopausal periods). In each group, subgroups of the Buryat and Russian populations were identified. The first group included 34 patients with T2DM of the reproductive period: 16 from the Buryat population and 18 from the Russian population. The second group consisted of 39 postmenopausal patients with T2DM: 17 from the Buryat population and 22 from the Russian population. The study of BMD in the lumbar spine (L1-L4), femoral neck (Neck), in the proximal femur (Total hip), trabecular bone score (TBS), serum osteocalcin (OC), N-terminal propeptide type 1 procollagen was carried out (P1NP), vitamin D 25 (OH), blood plasma type I collagen C-terminal telopeptide (β-Cross laps) and ionized calcium (iCa).Results: In female patients with T2DM of the reproductive age of the Buryat population, an increase in both markers of osteosynthesis P1NP (p=0.035), OC (p=0.047), and bone resorption β-Cross laps (p=0.040) was found relative to the similar group of the Russian population. In women with T2DM in the postmenopausal period of the Buryat population, there was also an increase in P1NP (p = 0.016), OC (p = 0.048), β-Cross laps (p = 0.020) compared with the group of postmenopausal women in the Russian population. Structural disorders, characterized by a decrease in TBS, were detected only in the postmenopausal period in female patients of the Buryat population compared to women in the Russian population (p = 0.029).Comparative analysis among women with T2DM of the Buryat population, depending on the functional state of the ovaries, showed that activation of bone remodeling with an increase in P1NP (p = 0.019), OC (p = 0.004) and β-Cross laps (p = 0.004) is characteristic of postmenopausal women accompanied by a decrease in BMD Neck (p = 0.006), BMD Total hip (p = 0.003), BMD L1-L4 (p = 0.049) and TBS (p = 0.020) relative to female patients with T2DM in the reproductive period.Conclusion: In women with T2DM in the Buryat population, both in the reproductive and postmenopausal periods, an increase in bone remodeling markers and BMD stability was found when compared with the corresponding groups of patients in the Russian population. The postmenopausal period was characterized by an additional decrease in TBS in patients with T2DM in the Buryat population relative to women in the Russian population.

Markers of bone remodeling in patients with surgical menopause undergoing hormone replacement therapy with Divigel

Twenty women with surgical menopause, 40-50 years of age, received hormonal replacement therapy with transdermic preparation Divigel during 24 months. On the background of therapy with Divigel we witnessed normalization of indeces of osteal remodelingconsiderable decrease pyridinoline and deoxypyridinoline, and elevation of alkaline phosphatase. Mineral density of bone tissue in the group of patients with surgical menopause waslowerin comparison with control (p0,01). Divigeltumedto exertprotective influence on the bone tissue inpatients with osteoporosis irrespective о f duration о f surgical menopause by the beginning of therapy.