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Original ArticlesNephrolithiasis
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Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones

Megan Prochaska, Eric Taylor, Anand Vaidya and Gary Curhan
CJASN August 2017, 12 (8) 1284-1290; DOI: https://doi.org/10.2215/CJN.01420217
Megan Prochaska
Divisions of *Renal Medicine and
†Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and
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Eric Taylor
†Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and
‡Division of Nephrology and Transplantation, Maine Medical Center, Portland, Maine
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Anand Vaidya
§Endocrinology, Diabetes, and Hypertension, and
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Gary Curhan
Divisions of *Renal Medicine and
†Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and
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    Table 1.

    Characteristics by reported low bone density from study midpoint (2003)

    CharacteristicNo Low Bone Density (n=57,338)Low Bone Density (n=3402)
    Age, yr48 (5)51 (4)
    Race, white55,491 (97)3331 (98)
    Body mass index, kg/m227.1 (6.3)24.5 (5.1)
    Postmenopausal18,604 (32)2192 (64)
    Bisphosphonate use95 (<1)282 (8)
    History of hypertension9788 (18)531 (16)
    History of diabetes1697 (3)65 (2)
    Family history of kidney stones8026 (14)535 (16)
    Thiazide use4038 (7)237 (7)
    Fluid intake, L/d1.9 (0.8)1.9 (0.8)
    Dietary calcium intake, mg/d949 (420)958 (438)
    Dietary potassium intake, mg/d3228 (1034)3250 (1017)
    Median calcium supplement (25%–75%), mg/d 450 (0, 1162)1000 (500, 1167)
    Total vitamin D intake, IU487 (320)679 (379)
    • Data are presented as N (%) with dietary intake and urinary factors presented as mean (SD) unless otherwise indicated.

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    Table 2.

    Age- and multivariable-adjusted relative risks for incident kidney stones by low bone density (1995–2013)

    No Low Bone DensityLow Bone DensityP Value
    Cases2302262
    Person-yr1,081,62098,240
    Age-adjusted RR1.0 (ref)1.24 (1.08, 1.42)0.002
    MV-adjusted RR1.0 (ref)1.39 (1.20, 1.62)<0.001
    • Data are presented as number of cases or person-years and RR (95% confidence interval). Multivariable model: Adjusted for age, body mass index, dietary factors (calcium, magnesium, potassium, sucrose, fructose, sodium, animal protein, vitamin D, vitamin C, phosphorus, alcohol, caffeine, total fluid), supplemental calcium intake, thiazide, family history of kidney stones, history of hypertension, history of diabetes mellitus, menopausal status, bisphosphonate use, and postmenopausal hormone use. RR, relative risk; ref, reference; MV, multivariable.

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    Table 3.

    Age- and multivariable-adjusted relative risks of incident kidney stones by bisphosphonate use among participants (n=17,075) with low bone density (2007–2013)

    No Bisphosphonate UseBisphosphonate UseP Value
    Cases15442
    Person-yr52,24020,494
    Age-adjusted RR1.0 (ref)0.69 (0.49, 0.97)0.03
    MV-adjusted RR1.0 (ref)0.68 (0.48, 0.98)0.03
    • Data are presented as number of cases or person-years and RR (95% confidence interval). Multivariable model: Adjusted for age, body mass index, dietary factors (calcium, magnesium, potassium, sucrose, fructose, sodium, animal protein, vitamin D, vitamin C, phosphorus, alcohol, caffeine, total fluid), supplemental calcium, thiazide, family history of kidney stones, history of hypertension, history of diabetes mellitus, menopausal status, and postmenopausal hormone use. RR, relative risk; ref, reference; MV, multivariable.

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    Table 4.

    Characteristics of participants who completed a 24-hour collection (n=2294)

    CharacteristicsNo Low Bone Density (n=1836)Low Bone Density (n=458)
    Age, yr53.6 (3.2)55.3 (2.8)
    Race, white1792 (98)449 (98)
    BMI, kg/m225.8 (4.9)23.6 (3.9)
    Postmenopausal1121 (61)379 (82)
    History of hypertension49 (3)11 (2)
    History of diabetes26 (1)9 (2)
    History of kidney stones46 (46 (2.5)16 (3.5)
    Family history of kidney stones296 (16)88 (19)
    Thiazide use37 (2)12 (3)
    Dietary intake
     Fluid intake, L/d1.7 (0.7)1.6 (0.7)
     Vitamin D intake, IU1006 (786)1340 (794)
     Calcium intake, mg/d959 (409)954 (414)
    Median calcium supplement (25%–75%), mg/d 500 (0–1000)800 (500–1024)
    Urinary factors
     Volume, L/d2.1 (0.9)2.1 (0.8)
     Calcium, mg/d200 (92)214 (98)
     Sodium, mEq/d139 (54)125 (52)
     Oxalate, mg/d31 (11)31 (12)
     Magnesium, mg/d107 (37)111 (43)
     Citrate, mg/d804 (283)789 (262)
     Potassium, mEq/d65 (20)65 (21)
     Sulfate, mEq/d38 (11)35 (11)
     Phosphorus, mg/d846 (244)766 (234)
     Ammonium, mmol/d30 (10)27 (9)
     Creatinine, mg/d1254 (206)1151 (190)
    • Categoric variables are presented as N (%) unless otherwise indicated. Continuous variables are presented as mean (SD) unless otherwise indicated. BMI, body mass index.

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    Table 5.

    Adjusted difference in 24-hour urinary calcium excretion for participants with history of low bone density (n=458) compared with participants without low bone density (n=1836)

    ModelDifference in Urinary Calcium (mg/d) for Low Bone Density95% CIP Value
    Age-adjusted166 to 260.002
    MV-adjusted101 to 190.02
    • Multivariable model: Adjusted for age, body mass index, bisphosphonate use, thiazide use, supplemental calcium intake, dietary calcium intake, total vitamin D intake, menopausal status, and urinary factors (volume, sodium, magnesium, citrate, potassium, sulfate, phosphorus, creatinine). 95% CI, 95% confidence interval; MV, multivariable.

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    Table 6.

    Adjusted difference in 24-hour urinary calcium excretion for participants with history of low bone density who were on a bisphosphonate (n=68) compared with participants who were not on a bisphosphonate (n=390)

    ModelDifference in Urinary Calcium (mg/d) for Bisphosphonate Use95% CIP Value
    Age-adjusted3−23 to 280.82
    MV-adjusted−2−25 to 200.83
    • Multivariable model: Adjusted for age, body mass index, thiazide use, supplemental calcium intake, dietary calcium intake, total vitamin D intake, menopausal status, and urinary factors (volume, sodium, magnesium, citrate, potassium, sulfate, phosphorus, creatinine). 95% CI, 95% confidence interval; MV, multivariable.

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Clinical Journal of the American Society of Nephrology: 12 (8)
Clinical Journal of the American Society of Nephrology
Vol. 12, Issue 8
August 07, 2017
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Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones
Megan Prochaska, Eric Taylor, Anand Vaidya, Gary Curhan
CJASN Aug 2017, 12 (8) 1284-1290; DOI: 10.2215/CJN.01420217

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Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones
Megan Prochaska, Eric Taylor, Anand Vaidya, Gary Curhan
CJASN Aug 2017, 12 (8) 1284-1290; DOI: 10.2215/CJN.01420217
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Keywords

  • body mass index
  • Bone Density
  • Calcium, Dietary
  • Cross-Sectional Studies
  • Diphosphonates
  • Epidemiologic Studies
  • female
  • follow-up studies
  • humans
  • kidney calculi
  • linear models
  • Proportional Hazards Models
  • prospective studies
  • risk assessment
  • risk factors
  • Thiazides

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