Skip to main content
SpringerLink
Log in

Bone matrix mineralization is preserved during early perimenopausal stage in healthy women: a paired biopsy study

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Bone matrix mineralization based on quantitative backscatter electron imaging remained unchanged during the first year of menopause in paired transiliac biopsy samples from healthy women. This suggests that the reported early perimenopausal reductions in bone mineral density are caused by factors other than decreases in the degree of mineralization.

Introduction

It is unknown whether perimenopausal loss of bone mass is associated with a drop in bone matrix mineralization.

Methods

For this purpose, we measured the bone mineralization density distribution (BMDD) by quantitative backscatter electron imaging (qBEI) in n = 17 paired transiliac bone biopsy samples at premenopausal baseline and 12 months after last menses (obtained at average ages of 49 ± 2 and 55 ± 2 years, respectively) in healthy women. For interpretation of BMDD outcomes, previously measured bone mineral density (BMD) and biochemical and histomorphometric markers of bone turnover were revisited for the present biopsy cohort.

Results

Menopause significantly decreased BMD at the lumbar spine (−4.5 %) and femoral neck (−3.8 %), increased the fasting urinary hydroxyproline/creatinine ratio (+60 %, all p < 0.01) and histomorphometric bone formation rate (+25 %, p < 0.05), but affected neither cancellous nor cortical BMDD variables (paired comparison p > 0.05). Mean calcium concentrations of cancellous (Cn.CaMean) and cortical bone (Ct.CaMean) were within normal range (p > 0.05 compared to established reference data). Ct.CaMean was significantly correlated with Cn.CaMean before (R = 0.81, p < 0.001) and after menopause (R = 0.80, p < 0.001) and to cortical porosity of mineralized tissue (Ct.Po.) after menopause (R = −0.57, p = 0.02).

Conclusions

Surprisingly, the BMDD was found not affected by the changes in bone turnover rates in this cohort. This suggests that the substantial increase in bone formation rates took place shortly before the second biopsy, and the bone mineralization changes lag behind. We conclude that during the first year after the last menses, the degree of bone matrix mineralization is preserved and does not contribute to the observed reductions in BMD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Recker RR (2011) Early postmenopausal bone loss and what to do about it. Ann N Y Acad Sci 1240:E26–30. doi:10.1111/j.1749-6632.2011.06371.x

    Article  CAS  PubMed  Google Scholar 

  2. Recker R, Lappe J, Davies K, Heaney K (2000) Characterization of perimenopausal bone loss: a prospective study. J Bone Miner Res 15:1965–1973

    Article  CAS  PubMed  Google Scholar 

  3. Khosla S, Melton LJ III, Riggs BL (2011) The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed? J Bone Miner Res 26:441–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Fratzl P, Roschger P, Fratzl-Zelman N, Paschalis EP, Phipps R, Klaushofer K (2007) Evidence that treatment with risedronate in women with postmenopausal osteoporosis affects bone mineralization and bone volume. Calcif Tissue Int 81:73–80

    Article  CAS  PubMed  Google Scholar 

  5. Rauch F, Schoenau E (2001) Changes in bone density during childhood and adolescence: an approach based on bone’s biological organization. J Bone Miner Res 16(4):597–604

    Article  CAS  PubMed  Google Scholar 

  6. Seeman E (2008) Bone quality: the material and structural basis of bone strength. J Bone Miner Metab 26:1–8

    Article  PubMed  Google Scholar 

  7. Qiu S, Rao DS, Palnitkar S, Parfitt AM (2006) Independent and combined contributions of cancellous and cortical bone deficits to vertebral fracture risk in postmenopausal women. J Bone Miner Res 21:1791–1796

    Article  PubMed  Google Scholar 

  8. Ciarelli TE, Fyhrie DP (2003) Parfitt AM Effects of vertebral bone fragility and bone formation rate on the mineralization levels of cancellous bone from white females. Bone 32(3):311–5

    Article  CAS  PubMed  Google Scholar 

  9. Akhter MP, Lappe JM, Davies KM, Recker RR (2007) Transmenopausal changes in the trabecular bone structure. Bone 41(1):111–6

    Article  CAS  PubMed  Google Scholar 

  10. Recker R, Lappe J, Davies KM, Heaney R (2004) Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients. J Bone Miner Res 19:1628–1633

    Article  PubMed  Google Scholar 

  11. Gamsjaeger S, Brozek W, Recker R, Klaushofer K, Paschalis EP (2014) Transmenopausal changes in trabecular bone quality. J Bone Miner Res 29(3):608–17

    Article  CAS  PubMed  Google Scholar 

  12. Boyde A, Compston JE, Reeve J, Bell KL, Noble BS, Jones SJ, Loveridge N (1998) Effect of estrogen suppression on the mineralization density of iliac crest biopsies in young women as assessed by backscattered electron imaging. Bone 22:241–250

    Article  CAS  PubMed  Google Scholar 

  13. Boivin G, Vedi S, Purdie DW, Compston JE (2005) Meunier PJ influence of estrogen therapy at conventional and high doses on the degree of mineralization of iliac bone tissue: a quantitative microradiographic analysis in postmenopausal women. Bone 36:562–567

    Article  CAS  PubMed  Google Scholar 

  14. Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV, Meunier PJ (2003) Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab 88(9):4199–205

    Article  CAS  PubMed  Google Scholar 

  15. Paschalis EP, Boskey AL, Kassem M, Eriksen EF (2003) Effect of hormone replacement therapy on bone quality in early postmenopausal women. J Bone Miner Res 18(6):955–9

    Article  CAS  PubMed  Google Scholar 

  16. Valenta A, Roschger P, Fratzl-Zelman N, Kostenuik PJ, Dunstan CR, Fratzl P, Klaushofer K (2005) Combined treatment with PTH (1-34) and OPG increases bone volume and uniformity of mineralization in aged ovariectomized rats. Bone 37:87–95

    Article  CAS  PubMed  Google Scholar 

  17. Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466

    Article  CAS  PubMed  Google Scholar 

  18. Polly BJ, Yuya PA, Akhter MP, Recker RR, Turner JA (2012) Intrinsic material properties of trabecular bone by nanoindentation testing of biopsies taken from healthy women before and after menopause. Calcif Tissue Int 90(4):286–93

    Article  CAS  PubMed  Google Scholar 

  19. Misof BM, Dempster DW, Zhou H, Roschger P, Fratzl-Zelman N, Fratzl P, Silverberg SJ, Shane E, Cohen A, Stein E, Nickolas TL, Recker RR, Lappe J, Bilezikian JP, Klaushofer K (2014) Relationship of bone mineralization density distribution (BMDD) in cortical and cancellous bone within the iliac crest of healthy premenopausal women. Calcif Tissue Int 95(4):332–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Parisien M, Cosman E, Morgan D, Schnitzer M, Liang X, Nieves J, Forese L, Luckey M, Meier D, Shen V, Lindsay R, Dempster DW (1997) Histomorphometric assessment of bone mass, structure, and remodeling: a comparison between healthy black and white premenopausal women. J Bone Miner Res 12:948–957

    Article  CAS  PubMed  Google Scholar 

  21. Cohen A, Recker RR, Lappe J, Dempster DW, Cremers S, McMahon DJ, Stein EM, Fleischer J, Rosen CJ, Rogers H, Staron RB, Lemaster J, Shane E (2012) Premenopausal women with idiopathic low-trauma fractures and/or low bone mineral density. Osteoporos Int 23:171–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dimai H, Linkhart T, Linkhart S, Donahue L, Beamer W, Rosen C, Farley J, Baylink D (1998) Alkaline phosphatase levels and osteoprogenitor cell numbers suggest bone formation may contribute to peak bone density differences between two inbred strains of mice. Bone 22:211–6

    Article  CAS  PubMed  Google Scholar 

  23. Bergman I, Loxley R (1970) The determination of hydroxyproline in urine hydrolysates. Clin Chem Acta 27:347–349

    Article  CAS  Google Scholar 

  24. Roschger P, Fratzl P, Eschberger J, Klaushofer K (1998) Validation of quantitative backscattered electron imaging for the measurement of mineral density distribution in human bone biopsies. Bone 23:319–326

    Article  CAS  PubMed  Google Scholar 

  25. Roschger P, Gupta HS, Berzlanovich A, Ittner G, Dempster DW, Fratzl P, Cosman F, Parisien M, Lindsay R, Nieves JW, Klaushofer K (2003) Constant mineralization density distribution in cancellous human bone. Bone 32:316–323

    Article  CAS  PubMed  Google Scholar 

  26. Borah B, Dufresne T, Nurre J, Phipps R, Chmielewski P, Wagner L, Lundy M, Bouxsein M, Zebaze R, Seeman E (2010) Risedronate reduces intracortical porosity in women with osteoporosis. J Bone Miner Res 25:41–47

    Article  CAS  PubMed  Google Scholar 

  27. Manolagas SC, O'Brien CA, Almeida M (2013) The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol 9(12):699–712. doi:10.1038/nrendo.2013.179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Han Z-H, Palnitkar S, Rao DS, Nelson D, Parfitt AM (1997) Effects of ethnicity and age or menopause on the remodeling and turnover of iliac bone: implications for mechanisms of bone loss. J Bone Miner Res 12:498–508

    Article  CAS  PubMed  Google Scholar 

  29. Rosenbrock H, Seifert-Klauss V, Kaspar S, Busch R, Luppa PB (2002) Changes of biochemical bone markers during the menopausal transition. Clin Chem Lab Med 40(2):143–51

    Article  CAS  PubMed  Google Scholar 

  30. Boivin G, Farlay D, Bala Y, Doublier A, Meunier PJ, Delmas PD (2009) Influence of remodeling on the mineralization of bone tissue. Osteoporos Int 20(6):1023–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Roschger P, Dempster DW, Zhou H, Paschalis EP, Silverberg SJ, Shane E, Bilezikian JP, Klaushofer K (2007) New observations on bone quality in mild primary hyperparathyroidism as determined by quantitative backscattered electron imaging. J Bone Miner Res 22:717–723

    Article  PubMed  Google Scholar 

  32. Ruffoni D, Fratzl P, Roschger P, Phipps R, Klaushofer K, Weinkamer R (2008) Effect of temporal changes in bone turnover on the bone mineralization density distribution: a computer simulation study. J Bone Miner Res 23:1905–14

    Article  CAS  PubMed  Google Scholar 

  33. Boivin G, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14(3):S19–S24

    PubMed  Google Scholar 

  34. Borah B, Ritman EL, Dufresne TE, Jorgensen SM, Liu S, Sacha J, Phipps RJ, Turner RT (2005) The effect of risedronate on bone mineralization as measured by micro-computed tomography with synchrotron radiation: correlation to histomorphometric indices of turnover. Bone 37(1):1–9

    Article  CAS  PubMed  Google Scholar 

  35. Zoehrer R, Roschger P, Fratzl P, Durchschlag E, Paschalis E, Phipps R, Klaushofer K (2006) Effects of 3- and 5-year treatment with risedronate on the bone mineral density distribution of cancellous bone in human iliac crest biopsies. J Bone Miner Res 21:1106–1112

    Article  CAS  PubMed  Google Scholar 

  36. Paschalis EP, Glass EV, Donley DW, Eriksen EF (2005) Bone mineral and collagen quality in iliac crest biopsies of patients given teriparatide: new results from the fracture prevention trial. J Clin Endocrinol Metab 90:4644–4649

    Article  CAS  PubMed  Google Scholar 

  37. Misof BM, Roschger P, Cosman R, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R (2003) Effects of intermittent parathyroid hormone administration on bone mineralization density distribution in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88:1150–1156

    Article  CAS  PubMed  Google Scholar 

  38. Misof BM, Paschalis EP, Blouin S, Fratzl-Zelman N, Klaushofer K, Roschger P (2010) Effects of 1 year of daily teriparatide treatment on iliacal bone mineralization density distribution (BMDD) in postmenopausal osteoporotic women previously treated with alendronate or risedronate. J Bone Miner Res 25(11):2297–303. doi:10.1002/jbmr.198

    Article  CAS  PubMed  Google Scholar 

  39. Roschger P, Misof B, Paschalis E, Fratzl P, Klaushofer K (2014) Changes in the degree of mineralization with osteoporosis and its treatment. Curr Osteoporos Rep 12(3):338–50. doi:10.1007/s11914-014-0218-z

    Article  PubMed  Google Scholar 

  40. Seeman E, Martin TJ (2015) Co-administration of antiresorptive and anabolic agents: a missed opportunity. J Bone Miner Res 30:753–64. doi:10.1002/jbmr.2496

    Article  CAS  PubMed  Google Scholar 

  41. Compston JE, Vedi S, Kaptoge S, Seeman E (2007) Bone remodeling rate and remodeling balance are not co-regulated in adulthood: implications for the use of activation frequency as an index of remodeling rate. J Bone Miner Res 22(7):1031–6

    Article  PubMed  Google Scholar 

  42. Rehman MT, Hoyland JA, Denton J, Freemont AJ (1994) Age related histomorphometric changes in bone in normal British men and women. J Clin Pathol 47(6):529–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Recker RR, Kimmel DB, Parfitt AM, Davies KM, Keshawarz N, Hinders S (1988) Static and tetracycline-based bone histomorphometric data from 34 normal postmenopausal females. J Bone Miner Res 3(2):133–44

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Daniela Gabriel, Petra Keplinger, Sonja Lueger, and Phaedra Messmer for sample preparation and qBEI measurements at the Bone Material Laboratory of the Ludwig Boltzmann Institute of Osteology, Vienna, Austria. This work was supported by the AUVA (Austrian Social Insurance for Occupational Risk), the WGKK (Social Health Insurance Vienna), and the SCOR (Specialized Center of Research) AR39221.

Author information

Authors and Affiliations

  1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Kundratstr. 37, A-1120, Vienna, Austria

    B. M. Misof, P. Roschger, S. Blouin & K. Klaushofer

  2. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA

    R. Recker

Authors
  1. B. M. Misof
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Roschger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Blouin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Recker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Klaushofer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. M. Misof.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Misof, B.M., Roschger, P., Blouin, S. et al. Bone matrix mineralization is preserved during early perimenopausal stage in healthy women: a paired biopsy study. Osteoporos Int 27, 1795–1803 (2016). https://doi.org/10.1007/s00198-015-3446-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-015-3446-x

Keywords

Search

Navigation