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

Megan Prochaska; Eric Taylor; Anand Vaidya; Gary Curhan

doi:10.2215/CJN.01420217

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Table 1.

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

Characteristic	No Low Bone Density (n=57,338)	Low Bone Density (n=3402)
Age, yr	48 (5)	51 (4)
Race, white	55,491 (97)	3331 (98)
Body mass index, kg/m²	27.1 (6.3)	24.5 (5.1)
Postmenopausal	18,604 (32)	2192 (64)
Bisphosphonate use	95 (<1)	282 (8)
History of hypertension	9788 (18)	531 (16)
History of diabetes	1697 (3)	65 (2)
Family history of kidney stones	8026 (14)	535 (16)
Thiazide use	4038 (7)	237 (7)
Fluid intake, L/d	1.9 (0.8)	1.9 (0.8)
Dietary calcium intake, mg/d	949 (420)	958 (438)
Dietary potassium intake, mg/d	3228 (1034)	3250 (1017)
Median calcium supplement (25%–75%), mg/d	450 (0, 1162)	1000 (500, 1167)
Total vitamin D intake, IU	487 (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 Density Low Bone Density P Value
Cases 2302 262
Person-yr 1,081,620 98,240
Age-adjusted RR 1.0 (ref) 1.24 (1.08, 1.42) 0.002
MV-adjusted RR 1.0 (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 Use Bisphosphonate Use P Value
Cases 154 42
Person-yr 52,240 20,494
Age-adjusted RR 1.0 (ref) 0.69 (0.49, 0.97) 0.03
MV-adjusted RR 1.0 (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)

Characteristics	No Low Bone Density (n=1836)	Low Bone Density (n=458)
Age, yr	53.6 (3.2)	55.3 (2.8)
Race, white	1792 (98)	449 (98)
BMI, kg/m²	25.8 (4.9)	23.6 (3.9)
Postmenopausal	1121 (61)	379 (82)
History of hypertension	49 (3)	11 (2)
History of diabetes	26 (1)	9 (2)
History of kidney stones	46 (46 (2.5)	16 (3.5)
Family history of kidney stones	296 (16)	88 (19)
Thiazide use	37 (2)	12 (3)
Dietary intake
Fluid intake, L/d	1.7 (0.7)	1.6 (0.7)
Vitamin D intake, IU	1006 (786)	1340 (794)
Calcium intake, mg/d	959 (409)	954 (414)
Median calcium supplement (25%–75%), mg/d	500 (0–1000)	800 (500–1024)
Urinary factors
Volume, L/d	2.1 (0.9)	2.1 (0.8)
Calcium, mg/d	200 (92)	214 (98)
Sodium, mEq/d	139 (54)	125 (52)
Oxalate, mg/d	31 (11)	31 (12)
Magnesium, mg/d	107 (37)	111 (43)
Citrate, mg/d	804 (283)	789 (262)
Potassium, mEq/d	65 (20)	65 (21)
Sulfate, mEq/d	38 (11)	35 (11)
Phosphorus, mg/d	846 (244)	766 (234)
Ammonium, mmol/d	30 (10)	27 (9)
Creatinine, mg/d	1254 (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)
Model Difference in Urinary Calcium (mg/d) for Low Bone Density 95% CI P Value
Age-adjusted 16 6 to 26 0.002
MV-adjusted 10 1 to 19 0.02
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)
Model Difference in Urinary Calcium (mg/d) for Bisphosphonate Use 95% CI P Value
Age-adjusted 3 −23 to 28 0.82
MV-adjusted −2 −25 to 20 0.83
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.