Anti-PTH monoclonal antibody, clone 216H8

Aldehyde dehydrogenase 2 (ALDH2) is the enzyme that oxidizes the acetaldehyde produced by alcohol metabolism. This variant not only affects the response to alcohol but is also associated with several diseases, such as esophageal cancer, myocardial infarction, and particularly osteoporosis. In our previous study, we reported that compared to wild-type (WT) mice, Aldh2 knockout (KO) mice naturally have a strong bone formation ability, and high expression of parathyroid hormone receptor (PTHR1) in osteocytes. The effect of the Aldh2 gene on bone metabolism in response to intermittent PTH treatment is unknown. The purpose of this study was to clarify the effect of the Aldh2 gene on the bone anabolic response to intermittent PTH treatment in ovariectomized mice. Female KO and WT mice were ovariectomized at 8 weeks of age. At 14 weeks of age, the KO and WT mice were divided into vehicle-treated (Veh) and PTH-treated (PTH) groups (i.e., the WT-Veh, WT-PTH, KO-Veh and KO-PTH groups). PTH (1-34) and vehicle were subcutaneously administered to each group at a dose of 40 mu g/kg body weight (BW) five times per week for 4 weeks. Micro-CT showed that the bone volume (BV), trabecular number (Tb.N), connectivity density (Conn.D), and cortical thickness (Ct.Th) values in the KO-PTH mice were significantly higher than those in the KO-Veh mice. Histomorphometric analysis showed that the BV, Tb.N, and mineral apposition rate (MAR) values in the KO-PTH group were significantly higher than those in the KO-Veh group. The mRNA expression level of PTHR1 in the KO-PTH group was significantly increased and that of p21 in the KO-PTH group was significantly decreased compared with the levels in the KO-Veh group. The expression of PTHR in osteocytes from the KO-PTH group was also significantly increased compared with that in osteocytes from the KO-Veh group. Furthermore, cell cultures revealed that the ALP+CFU-f/total CFU-f percentage was significantly higher in the KO-PTH group than in the KO-Veh group. We concluded that in ovariectomized Aldh2 KO mice, the bone anabolic response to intermittent PTH treatment was significantly enhanced compared to that in WT mice, which may be mediated by the high expression level of PTHR1.

Background: A low serum 25-hydroxyvitamin D (25(OH) D) concentration has been associated with a higher risk of type 2 diabetes mellitus (T2DM), especially in older people. Our aim in this randomized controlled trial was to evaluate the effect of vitamin D treatment on inflammatory markers in non-obese Lebanese patients with T2DM, living in Beirut, Lebanon. Methods: Non-Obese patients with T2DM (n= 88), deficient/insufficient in vitamin D, were randomly assigned into one of two groups-a treatment group receiving 30,000 IU cholecalciferol/week for a period of six months, and a placebo group. Serum concentrations of TNF-alpha, high-sensitivity C-reactive protein (hs-CRP), and Interleukin-6 (IL-6) were the primary outcomes. A homeostatic model of insulin resistance (HOMA-IR) was assessed, in addition to serum concentrations of fasting blood glucose (FBG), HbA1C, (25(OH) D), and PTH. Results: The vitamin D group showed higher blood levels of (25(OH) D) (p< 0.0001), and a significant reduction in hs-CRP and TNF-alpha concentrations (p< 0.0001) compared to placebo. The decrease perceived in IL-6 concentrations was not significant (p= 0.1). No significant changes were seen in FBG (p= 0.9) and HbA1c levels (p= 0.85). Conclusion: Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients with T2DM. Additional studies with a larger sample and a longer period are advised in this regard. This trial was registered at ClinicalTrial.gov; Identifier number: NCT 03782805.