Nephrolithiasis-associated bone disease: pathogenesis and treatment options

Abstract

Nephrolithiasis remains a formidable health problem in the United States and worldwide. A very important but underaddressed area in nephrolithiasis is the accompanying bone disease. Epidemiologic studies have shown that osteoporotic fractures occur more frequently in patients with nephrolithiasis than in the general population. Decreased bone mineral density and defects in bone remodeling are commonly encountered in patients with calcium nephrolithiasis. The pathophysiologic connection of bone defects to kidney stones is unknown. Hypercalciuria and hypocitraturia are two important risk factors for stone disease, and treatments with thiazide diuretics and alkali, respectively, have been shown to be useful in preventing stone recurrence in small prospective trials. However, no studies have examined the efficacy of these agents or other therapies in preventing continued bone loss in calcium stone formers. This manuscript reviews the epidemiology, pathophysiology, and potential treatments of bone disease in patients with nephrolithiasis.

Conflict of interest statement

DISCLOSURE

All the authors declared no competing interests.

Figures

Figure 1. Cumulative incidence of vertebral fracture among Rochester, Minnesota, residents following an initial episode of symptomatic nephrolithiasis

The solid line indicates observed. The dashed line indicates expected. Figure reprinted with permission by Melton et al.

Figure 2. Mechanisms of action of potential therapeutic agents

ECF, extracellular fluid; =inhibitory role; =stimulatory role.

Figure 3. The effect of thiazide/indapamide and K-Cit on BMD of the L2–L4 spine, femoral neck, and radial shaft of hypercalciuric kidney stone formers

Data are expressed as percentage of normal, matched for age and gender (Z-score). **Indicates P =0.001, †indicates P<0.001. Bars above the blocks represent mean±s.d. Figure reprinted with permission by Pak et al. BMD, bone mineral density; K-Cit, potassium citrate.