Higher rates of ultrasound synovial hypertrophy, bone erosion and power doppler signal in asymptomatic Brazilian elderly versus young adults: a cross-sectional study.

To evaluate the prevalence of musculoskeletal ultrasonography (MSUS) abnormalities in asymptomatic elderly individuals. A cross-sectional controlled study was conducted and MSUS of 23 joints (wrist, metacarpophalangeal-MCP, proximal interphalangeal-PIP, elbow, glenohumeral, hip, knee, ankle, and metatarsophalangeal-MTP joints) was performed in healthy individuals aged 18-29 (young, n = 32) and 60-80 years-old (elderly, n = 32). Quantitative synovial hypertrophy (SH) was measured in mm and a semiquantitative scoring system (0-3) was used to grade SH, power doppler (PD) and bone erosion (BE). Young and elderly participants were 26.2 ± 3.2 and 65.9 ± 4.4 years-old, respectively. As compared to the young participants, elderly individuals had higher SH values in 35% of the joint surfaces (P < 0.05), higher rates of scores 1-3 for SH at the dorsal surface of the 3rd MCP, palmar surface of the 2nd MCP, 2nd PIP, 3rd MCP and 3rd PIP and subtalar joints (17.2 vs. 1.6%, P = 0.002; 29.7 vs. 6.3%, P = 0.001; 12.5 vs. 1.6%, P = 0.016; 21.9 vs. 6.3%, P = 0.011; 21.9 vs. 7.8%, P = 0.025; and 24.2 vs. 6.3%, P = 0.005, respectively), BE at the radiocarpal, ulnocarpal, dorsal surface of the 2nd MCP and posterior area of the glenohumeral joints (10.9 vs. 1.6%, P = 0.028; 12.5 vs. 0%, P = 0.003; 9.4 vs. 0%, P = 0.012; and 29.7 vs. 10.9%, P = 0.008, respectively) and PD at the dorsal surface of the 2nd and 3rd MCP joints (9.4 vs. 0%; P = 0.012 and 7.8 vs. 0%; P = 0.023, respectively). BE scores ≥ 1 were more frequent in the elderly (P < 0.05) in 22 (88%) of the joint surfaces evaluated. MSUS abnormalities are more frequent in asymptomatic elderly individuals as compared to young subjects.

Intermittent PTH1-34 causes DNA and chromosome breaks in osteoblastic and nonosteoblastic cells.

Toxicological studies have demonstrated that intermittent PTH1-34 treatment is associated with an increased incidence of osteosarcoma in Fischer 344 rats. Comet and micronucleus (MN) tests, standard methods to evaluate genotoxic potential of drugs, were used to detect DNA and chromosome breaks, respectively, after PTH1-34 treatment. MC3T3 cells, primary osteoblast calvarial cells, and human osteoblasts were treated with PTH1-34 (50 and 100 nM) for 6 h/day for 21 days to mimic intermittent administration. Genotoxic assays were performed at 6 h and 7, 14, and 21 days. Osteoblasts extracted from bone marrow of mice treated with daily subcutaneous PTH1-34 injections (20 and 40 µg/kg) for 10 weeks as well as Hep-2, HeLa, and Hep-G2 cells were also tested. We observed a significant increase in DNA lesions and MN prevalence in human and murine osteoblasts treated with PTH1-34 compared to controls (P < 0.01). The effect observed in vitro and confirmed in vivo was time- and dose-dependent. For nonosteoblastic Hep-2 and HeLa cells we observed increased DNA damage and MN prevalence only later in the course of the protocol, after 21 days of treatment (P < 0.01). In Hep-G2 cells intermittent PTH1-34 did not induce DNA damage or chromosome breaks. Our results demonstrated that intermittent PTH increases DNA and chromosome breaks in osteoblasts. This genotoxic effect is attenuated in nonosteoblastic cells, and the ability to induce DNA damage is lost in cells with detoxification properties (HepG2 cells) tested in vitro.