gms | German Medical Science

Questionnaire: Intermittently administrated PTH and teriparatide (PTH 1-34) are currently being used as therapies for osteoporosis. Recent studies have demonstrated promoting effect of PTH on fracture healing in both healthy and estrogen deficient female rats. In present study we investigated for the first time the effect of PTH on bone healing in aged orchiectomized male rats or controls.

Methods: Thirty six Sprague-Dawley male rats were orchiectomized at 8-month of age. Twenty four rats were sham operated. After 12 weeks, when orchiectomized (Orx) rats developed osteoporotic changes, a bilateral transverse metaphyseal osteotomy of tibia was performed in all rats. Both tibia were exposed and completely osteotomized 7 mm distal to the knee surface. A 5-hole T-shaped titanium plate was fixed to the tibia with the aid of 4 screws. Thereafter, rats were divided into 5 groups (n=12): 1) sham vehicle, 2) sham PTH every day (PTH/d), 3) Orx vehicle, 4) Orx PTH every day (PTH/d), 5) Orx PTH every other day (PTH/2d). PTH was applied from the next day after osteotomy onward; dosage was 40 µg/kg BW. After 5-weeks, one tibia was analyzed by computed tomographical, biomechanical and histolomorphometrical analyses. Metaphyseal clips of contralateral tibia were used in analyses of mRNA expression of Alp1, Oc, Igf-1, Rankl, Opg and Col1α1 genes. Serum was collected. Body weight, weight of visceral organs and adipose tissue, food intake were recorded.

Results and Conclusions: Serum testosterone level dropped to not detectable level in Orx rats confirming orchiectomy. PTH effect in all rats: serum osteocalcin level enhanced in sham from 15 to 47 µg/L; in Orx: from 18 to 56 µg/L; in Orx PTH/2d it was 31 µg/L. Cortical and callus densities (Ct.BMD and Cl.BMD), callus area were increased (Cl.BMD: sham: 328 to 438 mg/cm3, Orx: 327 to 448 mg/cm3 in Orx PTH/d, 410 mg/cm3 in Orx PTH/2d). Serum alkaline phosphatase and biomechanical properties did not change significantly after PTH. In sham rats: rate of osseous bridging of osteotomy was enhanced (67% to 100%). In Orx rats: bone genes (Igf-1, Opg, Rankl) were up-regulated. Food intake, body weight, weight of visceral organs and adipose tissue were not affected by PTH.

PTH improved bone healing in both androgen-deficient and healthy aged male rats and showed no adverse systemic effect. Effect was less if PTH was applied every other day. Higher costs of daily administration seemed to be justified. The findings may show up trends for therapeutic treatment of male patients.