Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state

Abstract

In order to interpret bone turnover markers (BTMs), we need to establish healthy reference intervals. It is difficult to establish reference intervals for older women because they commonly suffer from diseases or take medications that affect bone turnover. The aims of this study were: (1) to identify diseases and drugs that have a substantial effect on BTMs; (2) to establish reference intervals for premenopausal and postmenopausal women; and (3) to examine the effects of other factors on BTMs in healthy postmenopausal women. We studied women aged 30-39 years (n=258) and women aged 55-79 years (n=2419) from a five-European centre population-based study. We obtained a nonfasting serum and second morning void urine samples at a single baseline visit. BTMs were measured using automated immunoassay analysers. BTMs were higher in patients with vitamin D deficiency and chronic kidney disease. Three or more BTMs were higher in women who were osteoporotic and at least two BTMs were lower in women who were oestrogen replete, taking osteoporosis treatments or having diseases known to affect bone turnover. These were used as exclusion criteria for selecting the populations for the reference intervals. The reference intervals for BTMs were higher in postmenopausal than premenopausal women. Levels of BTMs were not dependent on geographical location and increased with age.

Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: A case control study

“…Thereafter BTM return to premenopausal levels but increases with age (69). All BTM in an elevated state, measured in this thesis are associated with osteoporosis (70). Ivasaka et al found no difference in BTM measured shortly after fracture (within 2 days) compared with pre fracture data (71).…”

Biochemistry of the menopause

“…Results can vary with time of day, season, diet and exercise. Reference intervals for bone turnover markers across ethnic groups have been reported for example in UK and Europe, [147][148][149] China [150][151][152] and Japan. 153,154 In Table 7, representative reference intervals for bone markers pre-and postmenopause are summarized.…”

“…153,154 In Table 7, representative reference intervals for bone markers pre-and postmenopause are summarized. 148,[155][156][157][158] Serum activity of bone ALP increases with age 20,21,25 as does the serum and urine excretion of CTX, NTX excretion in urine serum PINP and osteeocalcin. 148,155 Results for CTX and PINP are method dependent; 159 therefore, repeated measurements in one patient should be performed with the same assay particularly if monitoring treatment.…”

Morning vs evening dosing of the cathepsin K inhibitor ONO-5334: effects on bone resorption in postmenopausal women in a randomized, phase 1 trial

“…Women with osteoporosis have decreased bone density and higher CTX-I levels than otherwise healthy women [ 41 ]. We have previously shown that baseline CTX-I levels are not predictive of how patients with osteoporosis respond to antiresorptive therapy with ONO-5334 [ 23 ].…”