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Published in: Osteoporosis International 2/2013

01-02-2013 | Original Article

Impaired bone mineralization accompanied by low vitamin D and secondary hyperparathyroidism in patients with femoral neck fracture

Authors: S. Seitz, T. Koehne, C. Ries, A. De Novo Oliveira, F. Barvencik, B. Busse, C. Eulenburg, T. Schinke, K. Püschel, J. M. Rueger, M. Amling, P. Pogoda

Published in: Osteoporosis International | Issue 2/2013

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Abstract

Summary

Although it is well established that a decrease in bone mass increases the risk of osteoporotic fractures, the proportion of fractures attributable to areal bone mineral density (BMD) is rather low. Here, we have identified bone mineralization defects together with low serum 25-hydroxyvitamin D (25-(OH) D) levels as additional factors associated with femoral neck fractures.

Introduction

Osteoporotic fractures of the femoral neck are associated with increased morbidity and mortality. Although it is well established that a decrease in bone mass increases the risk of osteoporotic fractures, the proportion of fractures attributable to areal BMD is rather low. To identify possible additional factors influencing femur neck fragility, we analyzed patients with femoral neck fracture.

Methods

We performed a detailed clinical and histomorphometrical evaluation on 103 patients with femoral neck fracture including dual-energy X-ray absorptiometry, laboratory parameters, and histomorphometric and bone mineral density distribution (BMDD) analyses of undecalcified processed biopsies of the femoral head and set them in direct comparison to skeletal healthy control individuals.

Results

Patients with femoral neck fracture displayed significantly lower serum 25-(OH) D levels and increased serum parathyroid hormone (PTH) compared to controls. Histomorphometric analysis revealed not only a decreased bone volume and trabecular thickness in the biopsies of the patients, but also a significant increase of osteoid indices. BMDD analysis showed increased heterogeneity of mineralization in patients with femoral neck fracture. Moreover, patients with femoral neck fracture and serum 25-(OH) D levels below 12 μg/l displayed significantly thinner trabecular bone.

Conclusion

Taken together, our data suggest that impaired bone mineralization accompanied by low serum 25-(OH) D levels is of major importance in the etiology of femoral neck fractures. Therefore, balancing serum 25-(OH) D levels and thereby normalizing PTH serum levels may counteract pronounced mineralization defects and might decrease the incidence of femoral neck fractures.
Literature
1.
go back to reference Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261PubMedCrossRef Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261PubMedCrossRef
2.
go back to reference Lane NE (2006) Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol 194:S3–11PubMedCrossRef Lane NE (2006) Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol 194:S3–11PubMedCrossRef
3.
go back to reference Mazess R, Collick B, Trempe J, Barden H, Hanson J (1989) Performance evaluation of a dual-energy x-ray bone densitometer. Calcif Tissue Int 44:228–232PubMedCrossRef Mazess R, Collick B, Trempe J, Barden H, Hanson J (1989) Performance evaluation of a dual-energy x-ray bone densitometer. Calcif Tissue Int 44:228–232PubMedCrossRef
4.
go back to reference Boehm HF, Eckstein F, Wunderer C, Kuhn V, Lochmueller EM, Schreiber K, Mueller D, Rummeny EJ, Link TM (2005) Improved performance of hip DXA using a novel region of interest in the upper part of the femoral neck: in vitro study using bone strength as a standard of reference. J Clin Densitom 8:488–494PubMedCrossRef Boehm HF, Eckstein F, Wunderer C, Kuhn V, Lochmueller EM, Schreiber K, Mueller D, Rummeny EJ, Link TM (2005) Improved performance of hip DXA using a novel region of interest in the upper part of the femoral neck: in vitro study using bone strength as a standard of reference. J Clin Densitom 8:488–494PubMedCrossRef
5.
go back to reference Bousson V, Le Bras A, Roqueplan F et al (2006) Volumetric quantitative computed tomography of the proximal femur: relationships linking geometric and densitometric variables to bone strength. Role for compact bone. Osteoporos Int 17:855–864PubMedCrossRef Bousson V, Le Bras A, Roqueplan F et al (2006) Volumetric quantitative computed tomography of the proximal femur: relationships linking geometric and densitometric variables to bone strength. Role for compact bone. Osteoporos Int 17:855–864PubMedCrossRef
6.
go back to reference Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner WS, Nevitt MC, Cummings SR (2003) BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Mineral Res 18:1947–1954CrossRef Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner WS, Nevitt MC, Cummings SR (2003) BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Mineral Res 18:1947–1954CrossRef
7.
go back to reference Black DM, Bouxsein ML, Marshall LM, Cummings SR, Lang TF, Cauley JA, Ensrud KE, Nielson CM, Orwoll ES (2008) Proximal femoral structure and the prediction of hip fracture in men: a large prospective study using QCT. J Bone Mineral Res 23:1326–1333CrossRef Black DM, Bouxsein ML, Marshall LM, Cummings SR, Lang TF, Cauley JA, Ensrud KE, Nielson CM, Orwoll ES (2008) Proximal femoral structure and the prediction of hip fracture in men: a large prospective study using QCT. J Bone Mineral Res 23:1326–1333CrossRef
8.
go back to reference Buitrago-Tellez CH, Bonnaire F, Schulze C, Gufler H, Honninger A, Kuner E, Langer M (1997) Quantitative CT assessment of the proximal femur. Experimental studies on its correlation with breaking load in femoral neck fractures. RöFö 167:627–632PubMed Buitrago-Tellez CH, Bonnaire F, Schulze C, Gufler H, Honninger A, Kuner E, Langer M (1997) Quantitative CT assessment of the proximal femur. Experimental studies on its correlation with breaking load in femoral neck fractures. RöFö 167:627–632PubMed
9.
go back to reference Huber MB, Carballido-Gamio J, Bauer JS, Baum T, Eckstein F, Lochmuller EM, Majumdar S, Link TM (2008) Proximal femur specimens: automated 3D trabecular bone mineral density analysis at multidetector CT—correlation with biomechanical strength measurement. Radiology 247:472–481PubMed Huber MB, Carballido-Gamio J, Bauer JS, Baum T, Eckstein F, Lochmuller EM, Majumdar S, Link TM (2008) Proximal femur specimens: automated 3D trabecular bone mineral density analysis at multidetector CT—correlation with biomechanical strength measurement. Radiology 247:472–481PubMed
10.
go back to reference Fazzalari N, Moore RJ, Manthey BA, Vernon-Roberts B (1989) Comparative study of iliac crest and proximal femur histomorphometry in normal patients. J Clin Pathol 42:745–748PubMedCrossRef Fazzalari N, Moore RJ, Manthey BA, Vernon-Roberts B (1989) Comparative study of iliac crest and proximal femur histomorphometry in normal patients. J Clin Pathol 42:745–748PubMedCrossRef
11.
go back to reference Amling M, Herden S, Posl M, Hahn M, Ritzel H, Delling G (1996) Heterogeneity of the skeleton: comparison of the trabecular microarchitecture of the spine, the iliac crest, the femur, and the calcaneus. J Bone Mineral Res 11:36–45CrossRef Amling M, Herden S, Posl M, Hahn M, Ritzel H, Delling G (1996) Heterogeneity of the skeleton: comparison of the trabecular microarchitecture of the spine, the iliac crest, the femur, and the calcaneus. J Bone Mineral Res 11:36–45CrossRef
12.
go back to reference Loveridge N, Power J, Reeve J, Boyde A (2004) Bone mineralization density and femoral neck fragility. Bone 35:929–941PubMedCrossRef Loveridge N, Power J, Reeve J, Boyde A (2004) Bone mineralization density and femoral neck fragility. Bone 35:929–941PubMedCrossRef
13.
go back to reference Zebaze RM, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E (2010) Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 375:1729–1736PubMedCrossRef Zebaze RM, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E (2010) Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 375:1729–1736PubMedCrossRef
14.
go back to reference Khosla S, Kleerekoper M (1999) Biochemical markers of bone turnover. In: Favus MG (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 4th edn. Lippincott Williams & Wilkins, Philadelphia Khosla S, Kleerekoper M (1999) Biochemical markers of bone turnover. In: Favus MG (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 4th edn. Lippincott Williams & Wilkins, Philadelphia
15.
go back to reference Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Mineral Res 2:595–610CrossRef Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Mineral Res 2:595–610CrossRef
16.
go back to reference Aaron JE, Makins NB, Francis RM, Peacock M (1984) Staining of the calcification front in human bone using contrasting fluorochromes in vitro. J Histochem Cytochem 32:1251–1261PubMedCrossRef Aaron JE, Makins NB, Francis RM, Peacock M (1984) Staining of the calcification front in human bone using contrasting fluorochromes in vitro. J Histochem Cytochem 32:1251–1261PubMedCrossRef
17.
go back to reference Compston JE, Vedi S, Webb A (1985) Relationship between toluidine blue-stained calcification fronts and tetracycline-labeled surfaces in normal human iliac crest biopsies. Calcif Tissue Int 37:32–35PubMedCrossRef Compston JE, Vedi S, Webb A (1985) Relationship between toluidine blue-stained calcification fronts and tetracycline-labeled surfaces in normal human iliac crest biopsies. Calcif Tissue Int 37:32–35PubMedCrossRef
18.
go back to reference Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466PubMedCrossRef Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466PubMedCrossRef
19.
go back to reference Roschger P, Plenk H Jr, Klaushofer K, Eschberger J (1995) A new scanning electron microscopy approach to the quantification of bone mineral distribution: backscattered electron image grey-levels correlated to calcium K alpha-line intensities. Scanning Microsc 9:75–86PubMed Roschger P, Plenk H Jr, Klaushofer K, Eschberger J (1995) A new scanning electron microscopy approach to the quantification of bone mineral distribution: backscattered electron image grey-levels correlated to calcium K alpha-line intensities. Scanning Microsc 9:75–86PubMed
20.
go back to reference Boyde A, Maconnachie E, Reid SA, Delling G, Mundy GR (1986) Scanning electron microscopy in bone pathology: review of methods, potential and applications. Scan Electron Microsc 4:1537–1554 Boyde A, Maconnachie E, Reid SA, Delling G, Mundy GR (1986) Scanning electron microscopy in bone pathology: review of methods, potential and applications. Scan Electron Microsc 4:1537–1554
21.
go back to reference Jones SJ, Glorieux FH, Travers R, Boyde A (1999) The microscopic structure of bone in normal children and patients with osteogenesis imperfecta: a survey using backscattered electron imaging. Calcif Tissue Int 64:8–17PubMedCrossRef Jones SJ, Glorieux FH, Travers R, Boyde A (1999) The microscopic structure of bone in normal children and patients with osteogenesis imperfecta: a survey using backscattered electron imaging. Calcif Tissue Int 64:8–17PubMedCrossRef
22.
go back to reference Lai JK, Lucas RM, Clements MS, Roddam AW, Banks E (2010) Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies. BMC Publ Health 10:331CrossRef Lai JK, Lucas RM, Clements MS, Roddam AW, Banks E (2010) Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies. BMC Publ Health 10:331CrossRef
23.
go back to reference Tsangari H, Findlay DM, Zannettino AC, Pan B, Kuliwaba JS, Fazzalari NL (2006) Evidence for reduced bone formation surface relative to bone resorption surface in female femoral fragility fracture patients. Bone 39:1226–1235PubMedCrossRef Tsangari H, Findlay DM, Zannettino AC, Pan B, Kuliwaba JS, Fazzalari NL (2006) Evidence for reduced bone formation surface relative to bone resorption surface in female femoral fragility fracture patients. Bone 39:1226–1235PubMedCrossRef
24.
go back to reference Priemel M, von Domarus C, Klatte TO et al (2009) Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res 25:305–312CrossRef Priemel M, von Domarus C, Klatte TO et al (2009) Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res 25:305–312CrossRef
25.
go back to reference Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501PubMedCrossRef Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501PubMedCrossRef
26.
go back to reference Fisher A, Srikusalanukul W, Davis M, Smith P (2010) Hip fracture type: important role of parathyroid hormone (PTH) response to hypovitaminosis D. Bone 47:400–407PubMedCrossRef Fisher A, Srikusalanukul W, Davis M, Smith P (2010) Hip fracture type: important role of parathyroid hormone (PTH) response to hypovitaminosis D. Bone 47:400–407PubMedCrossRef
27.
go back to reference Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD (2009) Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone 45:870–875PubMedCrossRef Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD (2009) Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone 45:870–875PubMedCrossRef
28.
go back to reference Madsen CM, Jorgensen HL, Lind B, Ogarrio HW, Riis T, Schwarz P, Duus BR, Lauritzen JB (2012) Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice. Injury (in press) Madsen CM, Jorgensen HL, Lind B, Ogarrio HW, Riis T, Schwarz P, Duus BR, Lauritzen JB (2012) Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice. Injury (in press)
29.
go back to reference 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 23:1905–1914PubMedCrossRef 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 23:1905–1914PubMedCrossRef
30.
go back to reference Busse B, Hahn M, Soltau M, Zustin J, Puschel K, Duda GN, Amling M (2009) Increased calcium content and inhomogeneity of mineralization render bone toughness in osteoporosis: mineralization, morphology and biomechanics of human single trabeculae. Bone 45:1034–1043PubMedCrossRef Busse B, Hahn M, Soltau M, Zustin J, Puschel K, Duda GN, Amling M (2009) Increased calcium content and inhomogeneity of mineralization render bone toughness in osteoporosis: mineralization, morphology and biomechanics of human single trabeculae. Bone 45:1034–1043PubMedCrossRef
Metadata
Title
Impaired bone mineralization accompanied by low vitamin D and secondary hyperparathyroidism in patients with femoral neck fracture
Authors
S. Seitz
T. Koehne
C. Ries
A. De Novo Oliveira
F. Barvencik
B. Busse
C. Eulenburg
T. Schinke
K. Püschel
J. M. Rueger
M. Amling
P. Pogoda
Publication date
01-02-2013
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 2/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-2011-0

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