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Annette Schlemmer, Christian Hassager, Juha Risteli, Leila Risteli, Signe B Jensen and Claus Christiansen

In order to determine whether bone turnover varies during the normal menstrual cycle, we measured biochemical markers of bone resorption (serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum alkaline phosphatase) in ten healthy premenopausal women every two or three days for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its nadir during the follicular phase and its peak during the luteal phase, and an overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic changes were observed in the urinary parameters of bone resorption or in the biochemical markers of bone formation. We conclude that sICTP, a new biochemical marker of bone resorption, undergoes small variations during a normal menstrual cycle in premenopausal women, whereas the biochemical markers of bone formation remain constant.

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Lars T. Jensen, Jens O.L. Jørgensen, Juha Risteli, Jens S. Christiansen and Ib Lorenzen

Abstract.

The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days compared with 2 IU/day (normal replacement dose) (p=0.04). Withdrawal of GH therapy for 14 days resulted in wider variation, but not significantly different from the levels at 2, 4 and 6 IU/day. A dose dependency was found regarding type III procollagen propeptide, showing significantly higher serum concentrations at a GH dose of 4 IU/day compared with 2 IU/day (p=0.001), and of 6 IU/day compared with 4 IU/day (p=0.001). Withdrawal of GH therapy resulted in significantly lower type III procollagen propeptide concentrations compared with those at a GH dose of 4 and 6 IU/day (p=0.03). Serum type III procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective tissue. Serum type I and type III procollagen propeptides may prove useful as monitors of GH therapy, especially regarding the GH dose levels in the individual patients.

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Vilhelmiina Parikka, ZhiQi Peng, Teuvo Hentunen, Juha Risteli, Teresa Elo, H Kalervo Väänänen and Pirkko Härkönen

Objective: Although the beneficial effects of estrogen on bone are well known, the roles of estrogen receptors (ERs) in mediating these effects are not fully understood.

Methods: To study the effects of long-term ERα deficiency, bone phenotype was studied in aged ERα knockout (ERKO) mice. In addition, ERKO osteoclasts and osteoblasts were cultured in vitro.

Design and results: Histomorphometric analysis showed that the trabecular bone volume and thickness were significantly increased and the rate of bone formation enhanced in both male and female ERKO mice in comparison to the wild-type animals. In ERKO males, however, the bones were thinner and their maximal bending strengths decreased. Consistent with previous reports, the bones of knockout mice, especially of female mice, were shorter than those of wild-type mice. In addition, the growth plates were totally absent in the tibiae of aged ERKO females, whereas the growth plate cartilages were detectable in wild-type females as well as in all the males. Analysis of cultured bone marrow cells from 10- to 12-week-old mice demonstrated that 17β-estradiol could stimulate osteoblastic differentiation of bone marrow cells derived from ERKO mice relatively to the same extent as those derived from wild-type mice. This was demonstrated by increases in synthesis of type I collagen, activity of alkaline phosphatase and accumulation of calcium in cultures. Total protein content was, however, reduced in ERKO osteoblast cultures.

Conclusions: These results show altered bone phenotype in ERKO mice and demonstrate the stimulatory effect of estrogen on osteoblasts even in the absence of full-length ERα.