The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality.
Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality.


BACKGROUND
The aim of the present study was to evaluate the effect of oral calcitonin on bone collagen maturation measured as the ratio between the degradation products of newly synthesized C-telopeptides of type I collagen (alphaalphaCTX) and mature isomerized betabetaCTX in postmenopausal women.


METHODS
Participants were from a phase II study. A total of 168 postmenopausal women were included and treated with placebo, 0.15, 0.4, 1, or 2.5 mg calcitonin daily. The non-isomerized alphaalphaCTX and isomerized betabetaCTX were measured in 24-hour urine samples obtained at baseline, and after 1 day, 1 month and 3 months of therapy.


RESULTS
Calcitonin, significantly and dose-dependently inhibited bone resorption by up to 50% as measured by alphaalphaCTX and isomerized betabetaCTX. Bone collagen maturation measured as the ratio between alphaalphaCTX and betabetaCTX remained unchanged during treatment with calcitonin.


CONCLUSIONS
Calcitonin dose-dependently and significantly reduced both alphaalphaCTX to betabetaCTX levels in urine without affecting the alphaalphaCTX to betabetaCTX ratio. This is in direct contrast to other anti-resorptive therapies, in which strong treatment-dependent effect on the endogenous age profile of bone has been observed. These data highlight that even though the treatments may have comparable effects on BMD, endogenous bone composition, which may be associated to bone quality, is strongly affected by the type of intervention, in which calcitonin display highly divergent effects from that of other anti-resorptives.
Karsdal
M A
MA
Nordic Bioscience A/S, Herlev Hovedgade 207, Herlev, 2730, Denmark. mk@nordicbioscience.com
Byrjalsen
I
I
Leeming
D J
DJ
Delmas
P D
PD
Christiansen
C
C
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D024042:Collagen Type I / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D010455:Peptides / Q000652:urine*; D017698:Postmenopause / Q000502:physiology / Q000652:urine
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C028815:salmon calcitonin; D002116:Calcitonin