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Letter
Associations of CTX-II with biochemical markers of bone turnover raise questions about its tissue origin: new insights from CHECK
  1. B de Klerk,
  2. F P J G Lafeber,
  3. W E van Spil
  1. Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to B de Klerk, Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; bo.deklerk{at}gmail.com

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The urinary level of the carboxy-terminal telopeptide of collagen type II (uCTX-II) currently is one of the most frequently used biochemical markers for assessing collagenolysis in articular cartilage during osteoarthritis. However, we published data suggesting release of CTX-II epitope from bone in Cohort Hip and Cohort Knee (CHECK), a large cohort of subjects with very early stage knee and/or hip osteoarthritis. As was observed for markers of bone metabolism, uCTX-II showed an abrupt increase in women aged 48–53 years that appeared to be attributable to menopause.1 Moreover, earlier work had already shown that uCTX-II has specifically strong associations with marker of bone metabolism as compared with other collagen-type markers.2

In response to our publications, Sprot3 proposed an alternative explanation for our findings: the increase of uCTX-II (expressed in ng/mmol creatine) would not be primarily attributable to increased uCTX-II (in the numerator), but rather to decreased levels of creatine (in the denominator), as women are known to undergo decreases of lean body mass during menopause.

To investigate this alternative explanation in our CHECK cohort study,1 ,2 serum creatine (sCreat) levels were assessed in all female CHECK subjects for whom sufficient blood was available after biochemical marker assessment (N=738). sCreat is generally dependent on two major components: glomerular filtration rate and muscle mass. Since glomerular filtration rate can be assumed to be constant in our generally healthy CHECK subjects aged 45–65 years,4 sCreat was interpreted as a marker of muscle mass in our subjects.

Associations of sCreat with demographic variables were investigated by linear regression. First, associations of sCreat with body mass index and age were investigated in all female subjects for whom sCreat and demographics were known (N=738). There appeared to be no association of sCreat with age (p=0.776), as is shown in table 1 and figure 1. Then, in addition, associations of sCreat with body mass index, age and menopausal status were investigated in women whose menopausal status was known (N=577).1 As was already suggested by the lack of an association between sCreat and age in all women, no association between sCreat and menopausal status was identified in women whose menopausal status was known (p=0.325), as is shown in table 2.

Table 1

Associations of serum creatine (sCreat) levels with body mass index (BMI), age and menopausal status (PMS=postmenopausal) were investigated in all female subjects for whom sCreat and demographics were known (N=738)

Table 2

Associations of sCreat with BMI and age in women with known menopausal status (N=577)

Figure 1

Serum creatine (sCreat) levels of different age categories in men and women.

Concluding, our data demonstrate that the menopausal increase of uCTX-II in female CHECK subjects is reasonably not based on lean body mass changes, but rather to actually increased release of CTX-II epitope, probably from bone (dependent changes).

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Footnotes

  • Contributors BdK wrote the letter, together with WEvS, using data from the CHECK study with approval of FPJGL. FPJGL helped directing the letter in the end.

  • Funding FPJGL reports grants from Dutch Arthritis Association, during the conduct of the study

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Local ethical committees of all participating medical centres.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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