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Archives of Osteoporosis
Published in: Archives of Osteoporosis 1/2020

Open Access 01-12-2020 | Bisphosphonate | Original Article

Alendronate use and bone mineral density gains in women with moderate-severe (stages 3B–5) chronic kidney disease: an open cohort multivariable and propensity score analysis from Funen, Denmark

Authors: M. Sanni Ali, Martin Ernst, Danielle E. Robinson, Fergus Caskey, Nigel K. Arden, Yoav Ben-Shlomo, Mads Nybo, Katrine H. Rubin, Andrew Judge, Cyrus Cooper, M. K. Javaid, Anne P. Hermann, Daniel Prieto-Alhambra

Published in: Archives of Osteoporosis | Issue 1/2020

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Abstract

Summary

Bisphosphonates are contraindicated in moderate-to-severe chronic kidney disease patients. However, they are used to prevent fragility fractures in patients with impaired kidney function, despite a lack of evidence on their effects on bone density in these patients. We demonstrated that Alendronate had a positive effect on bone in these patients.

Purpose

This study aimed to assess the association between alendronate use and bone mineral density (BMD) change in subjects with moderate-severe chronic kidney disease (CKD).

Methods

We created a cohort of CKD stage 3B–5 patients by linking all DXA-based measurements in the Funen area, Denmark, to biochemistry, national health registries and filled prescriptions. Exposure was dispensation of alendronate and the outcome was annualized percentage change in BMD at the femoral neck, total hip and lumbar spine. Individuals were followed from first BMD to the latest of subsequent DXA measurements. Alendronate non-users were identified using incidence density sampling and matched groups were created using propensity scores. Linear regression was used to estimate average differences in the annualized BMD.

Results

Use of alendronate was rare in this group of patients: propensity score matching (PSM) resulted in 71 alendronate users and 142 non-users with stage 3B–5 CKD (as in the 1 year before DXA). Whilst alendronate users gained an average 1.07% femoral neck BMD per year, non-users lost an average of 1.59% per annum. The PSM mean differences in annualized BMD were + 2.65% (1.32%, 3.99%), + 3.01% (1.74%, 4.28%) and + 2.12% (0.98%, 3.25%) at the femoral neck, total hip and spine BMD, respectively, all in favour of alendronate users.

Conclusion

In a real-world cohort of women with stage 3B–5 CKD, use of alendronate appears associated with a significant improvement of 2–3% per year in the femoral neck, total hip and spine BMD. More data are needed on the anti-fracture effectiveness and safety of bisphosphonate therapy in moderate-severe CKD.
Literature
1.
Anandarajah S, Tai T, de Lusignan S, Stevens P, O'Donoghue D, Walker M, Hilton S (2005) The validity of searching routinely collected general practice computer data to identify patients with chronic kidney disease (CKD): a manual review of 500 medical records. Nephrol Dial Transplant 20(10):2089–2096CrossRef
2.
Najar MS, Mir MM, Muzamil MM et al (2017) Prevalence of osteoporosis in patients with chronic kidney disease (stages 3–5) in comparison with age-and sex-matched controls: a study from Kashmir valley tertiary care center. Saudi J Kidney Dis Transpl 28(3):538–544CrossRef
3.
Nickolas TL, Stein EM, Dworakowski E, Nishiyama KK, Komandah-Kosseh M, Zhang CA, McMahon DJ, Liu XS, Boutroy S, Cremers S, Shane E (2013) Rapid cortical bone loss in patients with chronic kidney disease. J Bone Miner Res 28(8):1811–1820CrossRef
4.
Ensrud KE, Lui LY, Taylor BC, Ishani A, Shlipak MG, Stone KL, Cauley JA, Jamal SA, Antoniucci DM, Cummings SR, Osteoporotic Fractures Research Group (2007) Renal function and risk of hip and vertebral fractures in older women. Arch Gen Intern Med 167(2):133–139CrossRef
5.
Dooley AC, Weiss NS, Kestenbaum B (2008) Increased risk of hip fracture among men with CKD. Am J Kidney Dis 51(1):38–44CrossRef
6.
Maravic M, Ostertag A, Urena P, Cohen-Solal M (2016) Dementia is a major risk factor for hip fractures in patients with chronic kidney disease. Osteoporos Int 27(4):1665–1669CrossRef
7.
Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR, Wong C, Stehman-Breen C (2000) Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int 58(1):396–399CrossRef
8.
Hansen D, Olesen JB, Gislason GH, Abrahamsen B, Hommel K (2016) Risk of fracture in adults on renal replacement therapy: a Danish national cohort study. Nephrol Dial Transplant 31(10):1654–1662CrossRef
9.
Thomas R, Kanso A, Sedor JR (2008) Chronic kidney disease and its complications. Prim Care 35(2):329–344CrossRef
10.
Fujiwara S, Kasagi F, Masunari F (2003) Fracture prediction from bone mineral density in Japanese men and women. J Bone Miner Res 18(8):1547–1553CrossRef
11.
Jiang C, Giger ML, Kwak SM, Chinander MR, Martell JM, Favus MJ (2000) Normalized BMD as a predictor of bone strength. Acad Radiol 7(1):33–39CrossRef
12.
Iimori S, Mori Y, Akita W et al (2011) Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients—a single-center cohort study. Nephrol Dial Transplant 27(1):345–351CrossRef
13.
Yenchek RH, Ix JH, Shlipak MG, Bauer DC, Rianon NJ, Kritchevsky SB, Harris TB, Newman AB, Cauley JA, Fried LF, for the Health, Aging, and Body Composition Study (2012) Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol 7(7):1130–1136CrossRef
14.
West SL, Lok CE, Langsetmo L, Cheung AM, Szabo E, Pearce D, Fusaro M, Wald R, Weinstein J, Jamal SA (2015) Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res 30(5):913–919CrossRef
15.
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348(9041):1535–1541CrossRef
16.
Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix A (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the fracture intervention trial. JAMA 280(24):2077–2082CrossRef
17.
McClung M, Clemmesen B, Daifotis A, Gilchrist NL, Eisman J, Weinstein RS, Fuleihan G el-H, Reda C, Yates AJ, Ravn P (1998) Alendronate prevents postmenopausal bone loss in women without osteoporosis: a double-blind, randomized, controlled trial. Ann Intern Med 128(4):253–261CrossRef
18.
Siris E, Adler R, Bilezikian J et al (2014) The clinical diagnosis of osteoporosis: a position statement from the national bone health alliance working group. Osteoporos Int 25(5):1439–1443CrossRef
19.
McClung MR, Geusens P, Miller PD et al (2001) Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med 344(5):333–340CrossRef
20.
Hochberg MC, Ross PD, Black D, Cummings SR, Genant HK, Nevitt MC, Barrett-Connor E, Musliner T, Thompson D, for the Fracture Intervention Trial Research Group (1999) Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Arthritis Rheum 42(6):1246–1254CrossRef
21.
Ott MS (2012) Bisphosphonate safety and efficacy in chronic kidney disease. Kidney Int 82(8):833–835CrossRef
22.
Bouxsein ML, Delmas PD (2008) Considerations for development of surrogate endpoints for anti-fracture efficacy of new treatments in osteoporosis: a perspective. J Bone Miner Res 23(8):1155–1167CrossRef
23.
Schnitzer T, Bone H, Crepaldi GF et (2000) Therapeutic equivalence of alendronate 70 mg once weekly and alendronate 10 mg daily in the treatment of osteoporosis. Aging Clin Exp Res 12(1): 1-12
24.
Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Vandormael K, Lombardi A (2000) Alendronate for the treatment of osteoporosis in men. N Engl J Med 343(9):604–610CrossRef
25.
Saag KG, Emkey R, Schnitzer TJ et al (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med 339(5):92–299CrossRef
26.
27.
Levey AS, Stevens LA, Schmid CH, Zhang Y(L), Castro AF III, Feldman HI, Kusek JW, Eggers P, van Lente F, Greene T, Coresh J, for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612CrossRef
28.
Abrahamsen B, Jørgensen HL, Laulund AL et al (2014) Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures - the open thyro register cohort. J Bone Miner Res 29(9):2040–2050CrossRef
29.
Abrahamsen B, Jørgensen HL, Laulund AS, Nybo M, Bauer DC, Brix TH, Hegedüs L (2015) The excess risk of major osteoporotic fractures in hypothyroidism is driven by cumulative hyperthyroid as opposed to hypothyroid time: an observational register-based time-resolved cohort analysis. J Bone Miner Res 30(5):898–905CrossRef
30.
Rubin KH, Glintborg D, Nybo M, Andersen M, Abrahamsen B (2016) Fracture risk is decreased in women with polycystic ovary syndrome: a register-based and population-based cohort study. J Bone Miner Res 31(4):709–717CrossRef
31.
Praetorius K, Madsen CM, Abrahamsen B, Jørgensen HL, Lauritzen JB, Laulund ASB (2016) Low levels of hemoglobin at admission are associated with increased 30-day mortality in patients with hip f racture. Geriatr Orthop Surg Rehabil 7(3):115–120CrossRef
32.
Händel MN, Frederiksen P, Cohen A, Cooper C, Heitmann BL, Abrahamsen B (2017) Neonatal vitamin d status from archived dried blood spots and future risk of fractures in childhood: results from the D-tect study, a population-based case-cohort study. Am J Clin Nutr 106(1):155–161CrossRef
33.
Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR, FLEX Research Group (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (flex): a randomized trial. JAMA 296(24):2927–2938CrossRef
34.
35.
StataCorp (2017) Stata Statistical Software: Release 15 College Station, StataCorp LP, TX
36.
Prieto-Alhambra D, Lalmohamed A, Abrahamsen B, Arden NK, de Boer A, Vestergaard P, de Vries F (2014) Oral bisphosphonate use and total knee/hip implant survival: validation of results in an external population-based cohort. Arthritis Rheum 66(11):3233–3240CrossRef
37.
Harris ST, Watts NB, Genant HK, McKeever C, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 282(14):1344–1352CrossRef
38.
Rubin KH, Abrahamsen B, Hermann AP, Bech M, Gram J, Brixen K (2011) Prevalence of risk factors for fractures and use of DXA scanning in Danish women: a regional population-based study. Osteoporos Int 22(5):1401–1409CrossRef
39.
Cummings SR, Palermo L, Browner W, Marcus R, Wallace R, Pearson J, Blackwell T, Eckert S, Black D (2000) Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. JAMA 283(10):1318–1132CrossRef
40.
Riggs BL, Hodgson SF, O’fallon WM et al (1990) Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 322(12):802–809CrossRef
41.
Kinsella S, Murphy K, Breen M, O’Neill S, McLaughlin P, Coyle J, Bogue C, O’Neill F, Moore N, McGarrigle AM, Molloy MG, Maher MM, Eustace JA (2015) Comparison of single CT scan assessment of bone mineral density, vascular calcification and fat mass with standard clinical measurements in renal transplant subjects: the ABC heart study. BMC Nephrol 16(1):188CrossRef
Metadata
Title
Alendronate use and bone mineral density gains in women with moderate-severe (stages 3B–5) chronic kidney disease: an open cohort multivariable and propensity score analysis from Funen, Denmark
Authors
M. Sanni Ali
Martin Ernst
Danielle E. Robinson
Fergus Caskey
Nigel K. Arden
Yoav Ben-Shlomo
Mads Nybo
Katrine H. Rubin
Andrew Judge
Cyrus Cooper
M. K. Javaid
Anne P. Hermann
Daniel Prieto-Alhambra
Publication date
01-12-2020
Publisher
Springer London
Published in
Archives of Osteoporosis / Issue 1/2020
Print ISSN: 1862-3522
Electronic ISSN: 1862-3514
DOI
https://doi.org/10.1007/s11657-020-00746-z

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