Calcified Tissue International

, Volume 82, Issue 5, pp 341-347

First online:

Determinants of Bone Turnover Markers in Healthy Premenopausal Women

  • Silvano AdamiAffiliated withRheumatology Unit, University of Verona Email author 
  • , Gerolamo BianchiAffiliated withRheumatology Unit, Azienda Sanitaria 3
  • , Maria Luisa BrandiAffiliated withEndocrine Unit, University of Florence
  • , Sandro GianniniAffiliated withInternal Medicine, University of Padua
  • , Sergio OrtolaniAffiliated withOspedale Auxologico, Milan, Unità Operativa di Reumatologia e Malattie del Metabolismo Osseo, Istituto Auxologico Italiano Irccs
  • , Ombretta DiMunnoAffiliated withRhematology Unit, University of Pisa
  • , Bruno FredianiAffiliated withRhematology Unit, University of Siena
  • , Maurizio RossiniAffiliated withRheumatology Unit, University of Verona
  • , On behalf of the BONTURNO study groupAffiliated with

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Bone turnover markers (BTMs) are widely used for the management of osteoporosis, and the premenopausal reference range is the target value for the treatment of postmenopausal osteoporosis with antiresorbing agents. Three serum BTMs (serum C-telopeptide of type I collagen [CTX], osteocalcin [OC], and N-terminal propeptide of type I procollagen [P1NP]), serum calcium, creatinine, phosphate, magnesium, and follicle-stimulating hormone (FSH) were measured in 638 healthy premenopausal women aged 20–50 years. In 83 women on the contraceptive pill (CP), the levels of the three BTMs adjusted for all confounding factors were 14–26% lower (P < 0.005) than in non-CP users. In 18 women considered perimenopausal for serum FSH levels >30 IU/mL despite having regular menses, BTM levels were significantly higher than in age-matched women. This group of subjects and the women on the CP were excluded from further analysis. The three BTMs significantly decreased with advancing age and were negatively and independently correlated with body mass index (P < 0.001) and serum phosphate. In conclusion, we confirm that CP use is associated with significantly lower BTM values. An increase in BTM concentrations can be observed in perimenopausal women, i.e., women with normal menses but FSH levels >30 IU/mL. BTMs decrease substantially with advancing age, and this appears to be associated with changes in body weight and serum phosphate. New normative ranges for serum OC, CTX, and P1NP were identified; and our findings in general impose a redefinition of the criteria for establishing the normal ranges for BTMs.


Bone turnover marker Normative value Contraceptive pill Body weight Serum phosphate