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Acute development of cortical porosity and endosteal naive bone formation from the daily but not weekly short-term administration of PTH in rabbit.

ABSTRACT: Teriparatide [human parathyroid hormone (1-34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study developed 4 teriparatide regimens [20 ?g/kg/day (D20), 40 ?g/kg/day (D40), 140 ?g/kg/week (W140) and 280 ?g/kg/week (W280)] in the rabbit as a model animal with a well-developed Haversian system and osteons. The total weekly doses were equivalent in the low-dose groups (D20 and W140) and in the high-dose groups (D40 and W280). After the short-term (1 month) administration of TPDT, micro-CT, histomorphometry and three-dimensional second harmonic generation (3D-SHG) imaging to visualize the bone collagen demonstrated that daily regimens but not weekly regimens were associated with the significant development of cortical porosity and endosteal naïve bone formation by marrow fibrosis. We concomitantly monitored the pharmacokinetics of the plasma teriparatide levels as well as the temporal changes in markers of bone formation and resorption. The analyses in the present study suggested that the daily repeated administration of teriparatide causes more deleterious changes in the cortical microarchitecture than the less frequent administration of higher doses. The findings of the present study may have some implications for use of teriparatide in clinical treatment.

SUBMITTER: Yamane H

PROVIDER: S-EPMC5386260 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Acute development of cortical porosity and endosteal naïve bone formation from the daily but not weekly short-term administration of PTH in rabbit.

Yamane Hiroshi H Takakura Aya A Shimadzu Yukari Y Kodama Toshiyuki T Lee Ji-Won JW Isogai Yukihiro Y Ishizuya Toshinori T Takao-Kawabata Ryoko R Iimura Tadahiro T

PloS one 20170410 4

Teriparatide [human parathyroid hormone (1-34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study de ...[more]

PMID: 28394900

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Project description: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??l) or PTH 1-34 (43??g/kg/d) for 5- and 10-consecutive days. Trabecular bone microarchitecture (i.e., BV/TV [%], Tb.Th [?m], Tb.N [/mm], and Tb.Sp [?m]) was assessed in the distal femoral metaphysis and cortical bone parameters (i.e., Ct.Th [?m] and CSMI [mm4]) at the femoral mid-shaft. BMBV ossification (i.e., ossified vessel volume [OsVV, %] and ossified vessel thickness [OsV.Th, ?m]) was assessed in the medullary cavity of the femoral shaft. All parameters were determined by ?CT. 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??m vs. 12.1?±?1.4??m, 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??m) vs. CON (12.5?±?1.7??m). 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.

Dataset Information

Acute development of cortical porosity and endosteal naive bone formation from the daily but not weekly short-term administration of PTH in rabbit.

Publications

Acute development of cortical porosity and endosteal naïve bone formation from the daily but not weekly short-term administration of PTH in rabbit.

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