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Erschienen in: Osteoporosis International 5/2016

09.12.2015 | Original Article

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

verfasst von: B. M. Misof, P. Roschger, S. Blouin, R. Recker, K. Klaushofer

Erschienen in: Osteoporosis International | Ausgabe 5/2016

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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.
Literatur
2.
Zurück zum Zitat Recker R, Lappe J, Davies K, Heaney K (2000) Characterization of perimenopausal bone loss: a prospective study. J Bone Miner Res 15:1965–1973CrossRefPubMed Recker R, Lappe J, Davies K, Heaney K (2000) Characterization of perimenopausal bone loss: a prospective study. J Bone Miner Res 15:1965–1973CrossRefPubMed
3.
Zurück zum Zitat 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 26:441–451CrossRefPubMedPubMedCentral 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 26:441–451CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat 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 81:73–80CrossRefPubMed 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 81:73–80CrossRefPubMed
5.
Zurück zum Zitat 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):597–604CrossRefPubMed 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):597–604CrossRefPubMed
6.
Zurück zum Zitat Seeman E (2008) Bone quality: the material and structural basis of bone strength. J Bone Miner Metab 26:1–8CrossRefPubMed Seeman E (2008) Bone quality: the material and structural basis of bone strength. J Bone Miner Metab 26:1–8CrossRefPubMed
7.
Zurück zum Zitat 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 21:1791–1796CrossRefPubMed 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 21:1791–1796CrossRefPubMed
8.
Zurück zum Zitat 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):311–5CrossRefPubMed 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):311–5CrossRefPubMed
9.
Zurück zum Zitat Akhter MP, Lappe JM, Davies KM, Recker RR (2007) Transmenopausal changes in the trabecular bone structure. Bone 41(1):111–6CrossRefPubMed Akhter MP, Lappe JM, Davies KM, Recker RR (2007) Transmenopausal changes in the trabecular bone structure. Bone 41(1):111–6CrossRefPubMed
10.
Zurück zum Zitat 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 19:1628–1633CrossRefPubMed 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 19:1628–1633CrossRefPubMed
11.
Zurück zum Zitat Gamsjaeger S, Brozek W, Recker R, Klaushofer K, Paschalis EP (2014) Transmenopausal changes in trabecular bone quality. J Bone Miner Res 29(3):608–17CrossRefPubMed Gamsjaeger S, Brozek W, Recker R, Klaushofer K, Paschalis EP (2014) Transmenopausal changes in trabecular bone quality. J Bone Miner Res 29(3):608–17CrossRefPubMed
12.
Zurück zum Zitat 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 22:241–250CrossRefPubMed 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 22:241–250CrossRefPubMed
13.
Zurück zum Zitat 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 36:562–567CrossRefPubMed 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 36:562–567CrossRefPubMed
14.
Zurück zum Zitat 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):4199–205CrossRefPubMed 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):4199–205CrossRefPubMed
15.
Zurück zum Zitat 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):955–9CrossRefPubMed 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):955–9CrossRefPubMed
16.
Zurück zum Zitat 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 37:87–95CrossRefPubMed 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 37:87–95CrossRefPubMed
17.
Zurück zum Zitat Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466CrossRefPubMed Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466CrossRefPubMed
18.
Zurück zum Zitat 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):286–93CrossRefPubMed 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):286–93CrossRefPubMed
19.
Zurück zum Zitat 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):332–9CrossRefPubMedPubMedCentral 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):332–9CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat 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 12:948–957CrossRefPubMed 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 12:948–957CrossRefPubMed
21.
Zurück zum Zitat 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 23:171–82CrossRefPubMedPubMedCentral 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 23:171–82CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat 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 22:211–6CrossRefPubMed 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 22:211–6CrossRefPubMed
23.
Zurück zum Zitat Bergman I, Loxley R (1970) The determination of hydroxyproline in urine hydrolysates. Clin Chem Acta 27:347–349CrossRef Bergman I, Loxley R (1970) The determination of hydroxyproline in urine hydrolysates. Clin Chem Acta 27:347–349CrossRef
24.
Zurück zum Zitat 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 23:319–326CrossRefPubMed 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 23:319–326CrossRefPubMed
25.
Zurück zum Zitat 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 32:316–323CrossRefPubMed 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 32:316–323CrossRefPubMed
26.
Zurück zum Zitat 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 25:41–47CrossRefPubMed 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 25:41–47CrossRefPubMed
28.
Zurück zum Zitat 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 12:498–508CrossRefPubMed 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 12:498–508CrossRefPubMed
29.
Zurück zum Zitat 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):143–51CrossRefPubMed 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):143–51CrossRefPubMed
30.
Zurück zum Zitat 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):1023–6CrossRefPubMedPubMedCentral 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):1023–6CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat 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 22:717–723CrossRefPubMed 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 22:717–723CrossRefPubMed
32.
Zurück zum Zitat 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 23:1905–14CrossRefPubMed 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 23:1905–14CrossRefPubMed
33.
Zurück zum Zitat Boivin G, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14(3):S19–S24PubMed Boivin G, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14(3):S19–S24PubMed
34.
Zurück zum Zitat 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):1–9CrossRefPubMed 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):1–9CrossRefPubMed
35.
Zurück zum Zitat 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 21:1106–1112CrossRefPubMed 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 21:1106–1112CrossRefPubMed
36.
Zurück zum Zitat 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 90:4644–4649CrossRefPubMed 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 90:4644–4649CrossRefPubMed
37.
Zurück zum Zitat 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 88:1150–1156CrossRefPubMed 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 88:1150–1156CrossRefPubMed
38.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
41.
Zurück zum Zitat 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):1031–6CrossRefPubMed 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):1031–6CrossRefPubMed
42.
Zurück zum Zitat 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):529–34CrossRefPubMedPubMedCentral 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):529–34CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat 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):133–44CrossRefPubMed 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):133–44CrossRefPubMed
Metadaten
Titel
Bone matrix mineralization is preserved during early perimenopausal stage in healthy women: a paired biopsy study
verfasst von
B. M. Misof
P. Roschger
S. Blouin
R. Recker
K. Klaushofer
Publikationsdatum
09.12.2015
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 5/2016
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3446-x

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