Short-term intermittent PTH 1–34 administration and bone marrow blood vessel ossification in Mature and Middle-Aged C57BL/6 mice

Abstract

Intermittent parathyroid hormone (PTH) administration augments bone and progressive bone marrow blood vessel (BMBV) ossification occurs with advancing age. Since intermittent PTH administration augments bone, it may also serve to increase BMBV ossification. We assessed the influence of 5- and 10-days of intermittent PTH 1–34 administration on trabecular and cortical bone and BMBV ossification in mature (6–8 mon; n = 30) and middle-aged (10–12 mon; n = 30) male and female C57BL/6 mice. Mice were divided accordingly: control (CON) and 5-days (5dPTH) and 10-days (10dPTH) of PTH. Mice were given PBS (50 μl) or PTH 1–34 (43 μg/kg/d) for 5- and 10-consecutive days. Trabecular bone microarchitecture (i.e., BV/TV [%], Tb.Th [μm], Tb.N [/mm], and Tb.Sp [μm]) was assessed in the distal femoral metaphysis and cortical bone parameters (i.e., Ct.Th [μm] and CSMI [mm4]) at the femoral mid-shaft. BMBV ossification (i.e., ossified vessel volume [OsVV, %] and ossified vessel thickness [OsV.Th, μm]) was assessed in the medullary cavity of the femoral shaft. All parameters were determined by μCT. At this sample size, no gender-related differences were observed so female and male data were pooled. There were no main effects nor interactions for trabecular microarchitecture and Ct.Th. However, CSMI was larger (p < 0.05) in Middle-Age vs. Mature and larger (p < 0.05) in CON and 10dPTH vs. 5dPTH. OsVV tended (p = 0.057) to be higher (0.18 ± 0.04% vs. 0.09 ± 0.02%, respectively) and OsV.Th was higher (p < 0.05; 17.4 ± 1.6 μm vs. 12.1 ± 1.4 μm, respectively) in Middle-Aged vs. Mature mice. OsVV was not altered, but ossified vessels tended (p = 0.08) to be thicker in 10dPTH (17.6 ± 2.0 μm) vs. CON (12.5 ± 1.7 μm). No interactions were observed for OsVV and OsV.Th. In conclusion, this is the first report of ossified BMBV in C57BL/6 mice. The increased OsV.Th in Middle-Aged mice coincides with previous reports of increased OsVV in aged rats. The tendency of augmented OsV.Th in 10dPTH suggests that this treatment may ultimately impair the patency of bone marrow blood vessels.