The circadian rhythm of bone resorption: comparison between patients treated with teriparatide and patients with primary hyperparathyroidism
Maria Luchavova, Ivan Raska, Dana Michalska & Vit Zikan
Parathyroid hormone (PTH) has a biphasic effect on bone cells and can induce opposing responses resulting in both net bone loss and net bone formation. Patients with primary hyperparathyroidism (PHPT) lose the circadian rhythm for PTH and bone mass decreases. PTH administered intermittently resulting in increase in bone mass. We studied the differences in the circadian variability of bone turnover markers between women with PHPT and women with postmenopausal osteoporosis treated with teriparatide (TPD). Methods: Blood samples were obtained at 3-h intervals from 18 patients: postmenopausal women with osteoporosis treated with TPD given either in the morning (n=6) or evening (n=6), and elderly women with mild PHPT (n=6). Serum type I collagen C-telopeptide (βCTX), procollagen I N-terminal propeptide (P1NP), plasma intact PTH and serum calcium were measured. General linear model was used to determine circadian and group effect on measured variables (SPSS v.16). Results: There was a significant time effect on marker of bone resorption serum βCTX in TPD group, indicating presence of circadian variation. No circadian rhythm in serum βCTX was observed in patients with PHPT. There was also a significant group effect with the evening TPD group having daytime nadir and nocturnal peak of βCTX. The morning TPD blocked the morning decrease and the night peak of βCTX. Marker of bone formation P1NP showed no circadian rhythm in any group studied; however, absolute levels of P1NP were higher in patients treated with evening TPD as compared with either morning dosing regimen or PHPT. Conclusion: The timing of TPD treatment is able to significantly modify the circadian rhythm in serum βCTX in women with postmenopausal osteoporosis. More pronounced circadian variability in serum βCTX and higher levels of P1NP in the evening dosing regimen suggest that the circadian fluctuation in bone resorptive activity might be important to stimulate bone formation.