Bone-related hormones and bone turnover

Bone-related hormones and bone turnover


LASAC862

Contact: Natasja van Schoor

Background
Throughout life, bone is continuously being turned over by the two processes of bone resorption and bone formation.(1,2) These two processes are usually tightly coupled and result in the replacement of old bone by new bone, which is necessary for the maintenance of the mechanical integrity of the skeleton. Existing bone is resorbed by osteoclasts and new bone is formed by osteoblasts.(3,4). The rate of bone turnover can be assessed by measuring biochemical markers of bone formation and bone resorption in the blood or urine (see for review 5,6). In LASA, serum osteocalcin (OC) and deoxipyridinolin (DPD/Cr) were measured as bone markers. Circulating levels of play an important role in the bone remodeling complex. Therefore, circulating levels of systemic hormones, such as parathyroid hormone (PTH), serum 25-hydroxyvitamin D, sex hormones, and local factors, such as insulin-like growth factor 1 (IGF-1) were also determined in LASA.(7)

Measurements in LASA

Blood collection
Blood samples were obtained from respondents who participated in the second medical interview of LASA (1995/96), were born in 1930 and before (aged 65 years and older as of 1 January, 1996) and were living in Amsterdam, Zwolle and Oss and surroundings. At the visit in the hospital or health care centre, fasting urine and blood samples were obtained, centrifuged and stored at -20° or -70° until determination in 1997/1998.

Measurement procedure & variable information
Measurements of the hormone concentrations and markers of bone turnover were carried out at the Endocrine Laboratory of the VU University Medical Center (VUMC). Measurement of hormonal factors and biochemical markers included sex hormone-binding globulin (SHBG), , insulin-like growth factor 1 (IGF-1), osteocalcin (OC), deoxypyridinolin (DPD) and creatinine (Cr).
SHBG was measured by means of immuno radiometric assay (Orion Diagnostica, Espoo, Finland, and Incstar Corp., Stillwater, MN, USA, respectively). IGF-1 was determined by immunoradiometricassay after extraction (DSL, Webster, TX, USA). Serum levels of intact OC were measured using a immunoradiometric assay (Biosource Diagnostics, Fleurus, Belgium). Urinary excretions of DPD were measured by competitive immunoassay (ACS 180, Chiron Diagnostics, Emeryville, USA) Values were corrected for creatinine concentration in the same urine sample.
To estimate the coefficient of variation (CV), the measurements were measured twice in a subsample. %CV are available on request at the Endocrine Laboratory of the VUMC.
Table 1 shows the number of samples available, the lower limits of quantitation and mean values (SD), for hormones and biochemical parameters.

Table 1. Numbers, lower limit of quantitation and mean (SD) for biochemical parameters in blood and fasting urine.

Hormone /bone marker a

N

Lower limits of quantitation

mean (SD)

SHBG (nmol/l)

IGF-1 (nmol/l)

OC (nmol/l)

DPD

1320

1319

1319

1308

6 nM

1 nM

0.1 nM

15 nM

48.4 (22.4)

13.8 (5.2)

2.2 (1.1)

39.2 (29.2)

a SHBG=Sex Hormone Binding Globulin; IGF-1=insulin-like growth factor-1; OC=osteocalcin; DPD=deoxypyridinolin.

 

OC

intra-assay

inter-assay

 

mean

%CV

mean

%CV

level 1

0,9

5%

0,7

5%

level 2

> 1,7

3%

3,5

8%

level 3        

 

Availability of data per wave 

Numbers per wave 

SHBG (nmol/l)

 

B

C

 
2B*

G



3B*

All regions

 

1320

 

 

 

* 2B=baseline second cohort;
   3B=baseline third cohort

IGF-1 (nmol/l)

 

B

C

 
2B*

G



3B*

All regions

 

1319

 

 

 

* 2B=baseline second cohort;
   3B=baseline third cohort

OC (nmol/l)

 

B

C

 
2B*

G



3B*

All regions

 

1319

 

 

 

* 2B=baseline second cohort;
   3B=baseline third cohort

DPD (nmol/l) 

 

B

C

 
2B*

G



3B*

All regions

 

1308

 

 

 

* 2B=baseline second cohort;
   3B=baseline third cohort

Previous use in LASA
Research of Kuchuk et al. (2007) shows that low levels of bioE2 and bioT were found to be associated with high bone turnover, low QUS and BMD and high risk of osteoporotic fractures in both men and women. Dhonukshe-Rutten et al. (2005) stated that high Hcy and low vitamin B12 concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk. Pluijm et al. (2002) concluded bone markers and fractures were not associated with lower ApoE epsilon4 in either women or men.

  • Dhonukshe-Rutten, R.A.M., Pluijm, S.M.F., De Groot, L.C.P.G.M., Lips, P.T.A., Smit, J.H., Van Staveren, W.A. Homocysteine and Vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. Journal of Bone and Mineral Research 2005; 20, 6, 921-929.
  • Holvik K, van Schoor NM, Eekhoff EM, den Heijer M, Deeg DJ, Lips P, de Jongh R. Plasma osteocalcin levels as a predictor of cardiovascular disease in older men and women: a population-based cohort study. Eur J Endocrinol. 2014 Aug;171(2):161-70. doi: 10.1530/EJE-13-1044. Epub 2014 May 6.
  • Kuchuk, N.O., Van Schoor, N.M., Pluijm, S.M.F., Smit, J.H., De Ronde, W., Lips, P.T.A. The association of sex hormone levels with quantitative ultrasound, bone mineral denstiy, bone turnover and osteoporotic fractures in older men and women. Clinical Endocrinology 2007; 67, 295-303.
  • Limonard EJ, van Schoor NM, de Jongh RT, Lips P, Fliers E, Bisschop Ph. Osteocalcin and the pituitary-gonadal axis in older men: a population-based study. Clin Endocrinol (Oxf). 2105 May; 82(5): 753-9.
  • Oosterwerff MM, van Schoor NM, Lips P, Eekhoff EM. Osteocalcin as a predictor of the metabolic syndrome in older persons: a population-based study. Clin Endocrinol (Oxf). 2013 Feb;78(2):242-7. doi: 10.1111/j.1365-2265.2012.04391.x.
  • Pluijm, S.M.F., Dik, M.G., Jonker, C., Deeg, D.J.H., Van Kamp, G.J., Lips, P.T.A. Effects of gender and age on the association of apolipoprotein E epsilon 4 with bone mineral density, bone turnover and the risk of fractures in older people. Osteoporosis International 2002; 13, 701-709.
  • van Varsseveld NC, Sohl E, Drent ML, Lips P. Gender-specific associations of serum insulin-like growth factor-1 with bone health and fractures in older persons. J Clin Endocrinol Metab. 2015 Aug 31:jc20152549. [Epub ahead of print]
  • van Varsseveld NC, van Bunderen CC, Sohl E, Comijs HC, Penninx BW, Lips P, Drent ML. Serum insulin-like growth factor 1 and late-life depression: a population-based study. Psychoneuroendocrinology. 2015 Apr;54:31-40. doi: 10.1016/j.psyneuen.2015.01.014. Epub 2015 Jan 29.

References

  1. Lips P. Metabolic causes and prevention of hip fractures (PhD-thesis). Vrije Universiteit, Amsterdam, 1982.
  2. Parfitt AM. The coupling of bone formation to bone resorption: a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosis. Metab Bone Dis Relat Res 1982; 4: 1-6.
  3. Dempster DW, Lindsay R. Pathogenesis of osteoporosis. Lancet 1993; 341: 797-801.
  4. Delmas PD and Beaudreuil J. Biochemical markers of bone turnover in osteoporosis. J Clin Rheumatology 1997; 3: 211-216.
  5. Delmas PD, Eastell R, Garnero P, Seibell MJ, Stepan J. The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 2000; 11 (Suppl 6): S2-S17.
  6. Pluijm SMF. Predictors and consequences of falls and fractures in the elderly (PhD-thesis). Vrije Universiteit, Amsterdam, 2001.
  7. SMF Pluijm, M Visser, JH Smit, C Popp-Snijders, JC Roos, P Lips. Determinants of bone mineral density in older men and women: body composition as mediator. J Bone Miner Res 2001; 16: 2142-2151.