Bone metabolism in primary hypercalciuria

Primary Hypercalciuria (PH) is very frequently accompanied by some degrees of bone demineralization. The most frequent clinical condition in which this association has been studied is calcium nephrolithiasis. In these patients bone density has been reported to be very frequently low and increased susceptibility to fragility fractures has been described. One of the most important aspects is the very poor definition of this bone disease from a histomorphometric point of view. At present, the most common findings seem to range from those of a low bone turnover condition to an osteomalacic trait. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss has been mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism has been proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis has been strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNFare elevated in hypercalciuric patients. The effect of an excessive response to the acid load induced by dietary protein intake seems an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of PTH alterations, it has been proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissue. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss of PH patients, possibly via the effect of mild to moderate urinary phosphate loss, with secondary hypophosphatemia. In conclusion, bone loss is very common among PH patients. Even if most of the factors involved in this process have been identified, many aspects of this intriguing clinical condition remain to be elucidated.