Relationship between Urinary Calcium and Bone Mineral Density in Patients with Calcium Nephrolithiasis

Abstract

Calcium nephrolithiasis is associated with an increased risk of osteoporosis and fracture. Hypercalciuria has been assumed to be pathogenic for bone loss in kidney stone formers, although this association was shown in small cross-sectional studies. We explored the association of urine calcium with bone mineral density in kidney stone formers. We retrospectively studied bone mineral density in kidney stone formers. Excluded were subjects with hypercalcemia, chronic bowel disease, primary hyperparathyroidism, distal renal tubular acidosis or endogenous creatinine clearance less than 40 ml per minute. We included 250 males and 182 females subdivided into 145 who were estrogen treated and postmenopausal, and 37 who were nonestrogen treated and postmenopausal. We assessed the association of lumbar spine and femoral neck bone mineral density with 24-hour urine calcium on random and restricted diets, and while fasting using univariable and multivariable models adjusting for body mass index, urine sodium and sulfate. On multivariable analysis no significant association was found between urine calcium on a random or a restricted diet, or during fasting conditions and femoral neck or lumbar spine bone mineral density in men and estrogen treated women. In estrogen untreated women lumbar spine bone mineral density inversely correlated with urine calcium on the restricted diet (r = -0.38, p = 0.04 and adjusted r = -0.45, p = 0.02) and in the fasting state (r = -0.42, p = 0.05). Unlike in previous small cross-sectional studies we found no significant relationship between urine calcium and bone mineral density in a large group of calcium kidney stone formers. However, a significant inverse relationship was found in estrogen untreated kidney stone formers only. This study suggests that mechanism(s) other than hypercalciuria explain the lower bone mineral density and the higher fracture risk in patients who are kidney stone formers. It also highlights the role of estrogen on bone integrity.