Bone Disease in Primary Hypercalciuria

Abstract

SummaryPrimary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNF-α α are high 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 was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. 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 in 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.

Bone involvement in aldosteronism

“…Such a result actually reflects what has already been reported in healthy subjects from our country. (20) Although it is well known that hypercalciuria and secondary hyperparathyroidism can cause osteoporosis, (21) we believe that they do not fully explain the high prevalence of osteoporosis (73%) and vertebral fractures (46%) we observed in our group of PA patients. The expression of mineralcorticoid receptors on bone cells (6) could actually suggest a still unknown direct effect of mineralcorticoids on the skeletal tissue.…”

Plasma and urinary levels of cytokines in patients with idiopathic hypercalciuria

“…However, it is generally considered that IH is caused by an alteration in calcium homeostasis at sites where large amounts of calcium must be precisely controlled [5]. Several studies have shown decreased bone mineral density (BMD) in patients with IH [6][7][8][9][10][11][12][13][14][15][16][17][18]. This progressive decrease in bone mineral content suggests that osteoclasts and osteoblasts might play a key role in the chain of events leading to hypercalciuria.…”

Retrospective Review of Serum and Urinary Lithogenic Risk Factors in Patients With Osteoporosis and Osteopenia

“…A diet rich in sodium and animal proteins and low in calcium favors the development of calcium lithiasis and the loss of bone mineral density caused by an altered calciumphosphorous metabolism and the appearance of metabolic acidosis. 3,8 A range of studies have demonstrated that relapsing calcium renal lithiasis is associated with bone demineralization, [9][10][11] and calcium renal lithiasis is a risk factor for osteoporotic bone fracture. 12…”

“…A diet rich in sodium and animal proteins and low in calcium favors the development of calcium lithiasis and the loss of bone mineral density caused by an altered calciumphosphorous metabolism and the appearance of metabolic acidosis. 3,8 A range of studies have demonstrated that relapsing calcium renal lithiasis is associated with bone demineralization, [9][10][11] and calcium renal lithiasis is a risk factor for osteoporotic bone fracture. 12 The objective of this study was to examine and analyze differences in bone remodeling markers, lithogenic factors, and bone densitometry among the 3 groups of patients (controls, patients with relapsing calcium renal lithiasis, and patients with loss of bone mineral density without lithiasis).…”