Since the revision of the types of PH proposed by Levy and colleagues, the term “fasting hypercalciuria” has been used to identify patients who could not lower or normalize their urine calcium excretion appropriately after a restriction in dietary calcium consumption. As low bone density was more frequently reported in these patients, the presence of some conditions causing hypercalciuria and bone demineralization at the same time was suggested. Canadian Drugstore canadian medshop 247
Pacifici et al. firstly reported that some cytokines involved in the mechanisms regulating bone resorption may be involved in the pathogenesis of bone in patients with PH. They found that monocytes from patients with fasting hypercalciuria, but without the absorptive form, produced an exaggerated amount of interleukin-1, a well-known very potent stimulator of bone resorption processes, which in turn was correlated with a significant degree of bone demineralization. The role of cytokines in this setting was then confirmed by other reports. Weisinger and coworkers found that the production and mRNA expression of IL-1a from unstimulated peripheral blood mononuclear cells correlated with spinal bone loss in patients with PH and nephrolithiasis. In addition, the same cells produced an increased amount of IL-1a, IL-6, and TNF-a as compared to controls after stimulation with lipopolysaccharide (LPS). Since all these cytokines are considered local mediators of bone resorption, the Authors concluded that bone loss may largely depend upon these alterations in hypercalci- uric patients with calcium stones. Similar results were obtained by Ghazali et al., who found that IL-1 p, IL-6, TNF- a, and GM-CSF from peripheral blood monocytes were involved in the pathogenesis of bone loss in patients with PH. The consistency of all these results undoubtedly strengthens the importance of cytokines as pathogenetic factors of bone loss in PH. However, it remains to be elucidated if an overproduction of these cytokines from bone and bone marrow cells is also present. Indeed, even if it is believed that an altered cy- tokine secretion from peripheral mononuclear cells may in some way reflect a similar pattern in bone marrow, all these bone reabsorbing-substances are mainly considered local regulating factors of cell differentiation and function. In addition, no clear explanations were given for such an alteration in cytokine secretion in patients with PH and no differences in IL-1 p gene polymorphism were found between patients with or without PH.
Other factors are thought to be involved in bone alteration in PH. One of the most studied features is the effect of protein intake in these patients. Excessive protein intake, especially of animal origin, was found to sharply increase urine calcium excretion and bone resorption and lead to bone loss. The main responsible mechanism for these effects is the acid load produced by proteins, especially those rich in sulfur-containing amino acids. Accordingly, it was demonstrated that sulfate excretion and some markers of protein intake, such as urinary or serum urea, well correlate with bone turnover markers and density. In our study, we also found that a moderate protein restriction was accompanied by a proportional reduction in calcium excretion and bone turnover markers in patients with nephrolithiasis and PH. Since dietary protein excess was repeatedly reported in hypercalciuric stone formers and hypersensitivity to protein effects on bone was also suggested, normalization of protein intake is highly recommended in hypercalciuric patients.
No consistent data currently support the substantial role of cal- ciotropic hormones in the pathogenesis of bone loss in PH. Calcitriol was reported to be higher in PH patients than in controls and it was observed that this hormone may induce an increase in bone resorption. However, the elevation in cal- citriol levels was more frequently described in patients with absorptive hypercalciuria, whose bone density levels are generally normal or poorly diminished. In addition, Bataille et al. found that calcitriol levels have a protective rather than a damaging effect on bone mass in patients with PH and kidney stones. Apart from the very small proportion of patients that can be classified as having renal hypercalciuria, PTH levels are generally normal in PH patients and are not thought to have a significant role in the pathogenesis of bone loss in this setting.