Primary Hypercalciuria (PH) is very frequently accompanied by some degrees of bone demineralization. The most frequent clin- ical condition in which this association has been studied is cal- cium 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 im- portant aspects is the very poor definition of this bone disease from aic point of view. At present, the mostcommon findings seem to range from those of a low bone turnover condition to an osteomalacic trait. Many factors are in- volved in the complex relationships between bone loss and PH. Since bone loss has been mainly reported in patients with fast- ing 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 TNF- are elevated in hypercalciuric patients. The effect of an excessive response to the acid load induced by di- etary 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 absorp-tive hypercalciuria less frequently show bone disease and a re-
duction 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 intesti- nal calcium absorption in PH patients. Considering the absence of PTH alterations, it has been proposed that this is not a com- pensatory phenomenon, but probably the marker of disturbed
cell calcium transport, involving both intestinal and bone tis- sue. 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 conclu- sion, bone loss is very common among PH patients. Even if most of the factors involved in this process have been identi- fied, many aspects of this intriguing clinical condition remain to be elucidate
