Idiopathic hypercalciuria: Can we prevent stones and protect bones?

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Release date: January 1, 2018
Expiration date: December 31, 2018
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Idiopathic hypercalciuria increases the risk of urinary stones and osteoporosis. The aim of this review is to delineate our current understanding of idiopathic hypercalciuria in the context of bone health, specifically its definition, causes, epidemiology, laboratory evaluation, and potential treatments.


  • Idiopathic hypercalciuria is common in patients with kidney stones and is also present in up to 20% of postmenopausal women with osteoporosis but no history of kidney stones.
  • Idiopathic hypercalciuria has been directly implicated as a cause of loss of trabecular bone, especially in men. But reversing the hypercalciuria in this condition has not been definitively shown to diminish fracture incidence.
  • Patients with kidney stones who have low bone mass and idiopathic hypercalciuria should increase their daily fluid intake, follow a diet low in salt and animal protein, and take thiazide diuretics to reduce the risk of further calcium stone formation. Whether this approach also improves bone mass and strength and reduces fracture risk in this patient group requires further study.



A 65-year-old woman was recently diagnosed with osteoporosis after a screening bone mineral density test. She has hypertension (treated with lisinopril), and she had an episode of passing a kidney stone 10 years ago. A 24-hour urine study reveals an elevated urinary calcium level.

What should the physician keep in mind in managing this patient?


Many potential causes of secondary hypercalciuria must be ruled out before deciding that a patient has idiopathic hypercalciuria, which was first noted as a distinct entity by Albright et al in 1953.1 Causes of secondary hypercalciuria include primary hyperparathyroidism, hyperthyroidism, Paget disease, myeloma, malignancy, immobility, accelerated osteoporosis, sarcoidosis, renal tubular acidosis, and drug-induced urinary calcium loss such as that seen with loop diuretics.

Idiopathic hypercalciuria is identified by the following:

  • Persistent hypercalciuria despite normal or restricted calcium intake2,3
  • Normal levels of parathyroid hormone (PTH), phosphorus, and 1,25-dihydroxy-vitamin D (the active form of vitamin D, also called calcitriol) in the presence of hypercalciuria; serum calcium levels are also normal.

An alias for idiopathic hypercalciuria is “fasting hypercalciuria,” as increased urinary calcium persists and sometimes worsens while fasting or on a low-calcium diet, with increased bone turnover, reduced bone density, and normal serum PTH levels.4,5

Mineral loss from bone predominates in idiopathic hypercalciuria, but there is also a minor component of intestinal hyperabsorption of calcium and reduced renal calcium reabsorption.6 Distinguishing among intestinal hyperabsorptive hypercalciuria, renal leak hypercalciuria, and idiopathic or fasting hypercalciuria can be difficult and subtle. It has been argued that differentiating among hypercalciuric subtypes (hyperabsorptive, renal leak, idiopathic) is not useful; in general clinical practice, it is impractical to collect multiple 24-hour urine samples in the setting of controlled high- vs low-calcium diets.


Calcium is an important component in many physiologic processes, including coagulation, cell membrane transfer, hormone release, neuromuscular activation, and myocardial contraction. A sophisticated system of hormonally mediated interactions normally maintains stable extracellular calcium levels. Calcium is vital for bone strength, but the bones are the body’s calcium “bank,” and withdrawals from this bank are made at the expense of bone strength and integrity.

Renal stones

Patients with idiopathic hypercalciuria have a high incidence of renal stones. Conversely, 40% to 50% of patients with recurrent kidney stones have evidence of idiopathic hypercalciuria, the most common metabolic abnormality in “stone-formers.”7,8 Further, 35% to 40% of first- and second-degree relatives of stone-formers who have idiopathic hypercalciuria also have the condition.9 In the general population without kidney stones and without first-degree relatives with stones, the prevalence is approximately 5% to 10%.10,11

Bone loss

People with idiopathic hypercalciuria have lower bone density and a higher incidence of fracture than their normocalciuric peers. This relationship has been observed in both sexes and all ages. Idiopathic hypercalciuria has been noted in 10% to 19% of otherwise healthy men with low bone mass, in postmenopausal women with osteoporosis,10–12 and in up to 40% of postmenopausal women with osteoporotic fractures and no history of kidney stones.13


Urinary calcium excretion

Heaney et al14 measured 24-hour urinary calcium excretion in a group of early postmenopausal women, whom he divided into 3 groups by dietary calcium intake:

  • Low intake (< 500 mg/day)
  • Moderate intake (500–1,000 mg/day)
  • High intake (> 1,000 mg/day).

In the women who were estrogen-deprived (ie, postmenopausal and not on estrogen replacement therapy), the 95% probability ranges for urinary calcium excretion were:

  • 32–252 mg/day (0.51–4.06 mg/kg/day) with low calcium intake
  • 36–286 mg/day (0.57–4.52 mg/kg/day) with moderate calcium intake
  • 45–357 mg/day (0.69–5.47 mg/kg/day) with high calcium intake.

For estrogen-replete women (perimenopausal or postmenopausal on estrogen replacement), using the same categories of dietary calcium intake, calcium excretion was:

  • 39–194 mg/day (0.65–3.23 mg/kg/day) with low calcium intake
  • 54–269 mg/day (0.77–3.84 mg/kg/day) with moderate calcium intake
  • 66–237 mg/day (0.98–4.89 mg/kg/day) with high calcium intake.

In the estrogen-deprived group, urinary calcium excretion increased by only 55 mg/day per 1,000-mg increase in dietary intake, though there was individual variability. These data suggest that hypercalciuria should be defined as:

  • Greater than 250 mg/day (> 4.1 mg/kg/day) in estrogen-replete women
  • Greater than 300 mg/day (> 5.0 mg/kg/day) in estrogen-deprived women.

Urinary calcium-to-creatinine ratio

Use of a spot urinary calcium-to-creatinine ratio has been advocated as an alternative to the more labor-intensive 24-hour urine collection.15 However, the spot urine calcium-creatinine ratio correlates poorly with 24-hour urine criteria for hypercalciuria whether by absolute, weight-based, or menopausal and calcium-adjusted definitions.

Importantly, spot urine measurements show poor sensitivity and specificity for hypercalciuria. Spot urine samples underestimate the 24-hour urinary calcium (Bland-Altman bias –71 mg/24 hours), and postprandial sampling overestimates it (Bland-Altman bias +61 mg/24 hours).15


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