Skip to main content
SpringerLink
Log in

Idiopathic hypercalciuria: O −2 NO relationship and altered bone metabolism

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

The pathogenesis of idiopathic hypercalciuria (IH) has not been elucidated yet, but a correlation between IH and altered bone metabolism has been proposed. Since nitric oxide (NO) regulates osteoclasts’ bone resorption, a possible role for NO can be suggested. In this study we evaluated iNOS gene expression by reverse transcription of mRNA from monocytes, followed by polymerase chain reaction in patients with IH subdivided into fasting (FH) and absorptive (AH) hypercalciuria. Since superoxide (O −2 ), which metabolizes NO, is overproducted by osteoclasts during bone resorption, peroxynitrite plasma level was evaluated as index of O −2 . Vertebral BMD in IH as a whole group was lower vs controls (C) (Z score=-1.78±0.2 vs 0.51±0.25, p<0.001), but only FH patients showed a reduced bone density (2.13±0.18 vs 0.51±0.25, p<0.0001). PTH and calcitriol were not different. FH showed an increase in b-ALP vs AH and C (41.1±2.6 vs 30.1±3.9 vs 26.6±3.6 U/l p<0.02), and higher uHP, either on NCD (17.7±1.6 vs 11.4±1.3 mg/g uCr, p<0.04) or after LCD (26.7±2.5 vs 16.7±1.9, p<0.01). Cells from FH patients, but not from both AH patients and C, expressed iNOS. Peroxynitrite plasma level was elevated in FH (0.30±0.07) μmol/l while not detectable in AH and C. This study confirms an altered bone metabolism only in FH which shows an abnormal NO system. The increased iNOS gene expression in FH, in fact, points toward an altered NO system’s activity downstream the generation of NO. A possible interaction of NO with O −2 , which breaks down NO, and the role of this interaction in the pathophysiology of IH is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pak C.Y.C., Britton F., Peterson R., Ward D., Northcutt C., Breslau N.A., McGuire J., Sakhaee K., Bush S., Nicar M., Norman D.A., Peters P. Ambulatory evaluation of nephrolithiasis. Classification, clinical presentation and diagnostic criteria. Am. J. Med. 1980, 69: 19–30.

    Article  CAS  PubMed  Google Scholar 

  2. Coe F.L., Favus M.J. Disorders of stone formation. In: Brenner B.M., Rector F.C. Jr. (Eds.), The Kidney, ed. 2. W.B. Saunders, Philadelphia, 1982, 1981, p. 1950.

    Google Scholar 

  3. Giannini S., Nobile M., Castrignano R., Pati T., Tasca A., Villi G., Pellegrini F., D’Angelo A. Possible link between vitamin D and hyperoxaluria in patients with renal stone disease. Clin. Sci. 1993, 84: 51–54.

    CAS  PubMed  Google Scholar 

  4. Burckhardt P., Jaeger P. Secondary hyperparathyroidism in idiopathic renal hypercalciuria: fact or theory. J. Clin. Endocrinol. Metab. 1981, 3: 550–555.

    Article  Google Scholar 

  5. Pacifici R., Rothstein M., Rifas L., Lan K.H., Baylink D.J., Avioli L.V., Hruska U. Increased monocyte interleukin-1 activity and decreased vertebral bone density in patients with fasting idiopathic hypercalciuria. J. Clin. Endocrinol. Metab. 1990, 71: 138–145.

    Article  CAS  PubMed  Google Scholar 

  6. Messa P., Mioni G., Franzon R., Messa M., Cruciatti A., Giannini S., D’Angelo A. Factors affecting fasting urinary calcium excretion in stone former patients on different dietary calcium intake. Scanning Microsc. 1992, 6: 239–246.

    CAS  PubMed  Google Scholar 

  7. Giannini S., Nobile M., Sartori L., CaIò L., Tasca A., Dalle Carbonare L., Ciuffreda M., D’Angelo A., Pagano F., Crepaldi G. Bone density and skeletal metabolism are altered in idiopathic hypercalciuria. Clin. Nephrol. 1998, 50: 94–100.

    CAS  PubMed  Google Scholar 

  8. Maclntyre J., Zaidi M., Towhibdul A., Datta H., Moonga B., Lidsbury P., Hecker M., Vane J. Osteoclastic inhibition: an action of nitric oxide not mediated by cGMP. Proc. Natl. Acad. Sci. USA 1991, 88: 2936–2941.

    Article  Google Scholar 

  9. Collin-Osdoby P., Nickols G.A., Osdoby P. Bone cell function, regulation and communication: a role for nitric oxide. J. Cell. Biochem. 1995, 57: 399–408.

    Article  CAS  PubMed  Google Scholar 

  10. van’t Hof R.J., Ralston S.H. Cytokine-induced nitric oxide inhibits bone resorption by inducing apoptosis of osteoclast progenitors and suppressing osteoclast activity. J. Bone Min. Res. 1997, 11: 1797–1804.

    Article  Google Scholar 

  11. Gay C. Osteoclast ultrastructure and enzyme histochemistry. Functional implications. In: Rifkin B., Gay C. (Eds.), Biology and physiology of the osteoclast. CRC Press, Boca Raton, 1992, p. 130.

    Google Scholar 

  12. Horton M.A., Helfrich M.H. Antigenic markers of osteoclasts. In: Rifkin B., Gay C. (Eds.), Biology and physiology of the osteoclast. CRC Press, Boca Raton, 1992, p. 34.

    Google Scholar 

  13. Reiling N., Ulmer A.J., Duchrow M., Ernst M., Flad H.D., Hauschildt S. Nitric oxide synthase: mRNA expression of different isoforms in human monocytes/macrophages. Eur. J. Immunol. 1994, 24: 1941–1944.

    Article  CAS  PubMed  Google Scholar 

  14. Rosalki S.B., Foo A.Y. Two new methods for separating and quantifying bone and liver alkaline phosphatase isoenzymes in plasma. Clin. Chem. 1984, 3: 1182–1186.

    Google Scholar 

  15. CaIò L., Davis P.A., Rigotti P., Milani M., Cantaro S., Marchini F., D’Angelo A., Antonello A. ecNOS overexpression in CsA treated renal transplant patients. Transpl. Proc. 1998, 30: 2012–2013.

    Article  Google Scholar 

  16. CaIò L., Davis P.A., Milani M., Cantaro S., Antonello A., Favaro S., D’Angelo A. Increased endothelial nitric oxide synthase mRNA level in Bartter’s and Gitelman’s syndrome. Relationship to vascular reactivity. Clin. Nephrol. 1999, 1: 10–17.

    Google Scholar 

  17. Kaur H., Halliwell B. Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett. 1994, 350: 9–12.

    Article  CAS  PubMed  Google Scholar 

  18. Borghi L., Meschi T., Guerra A., Maninetti L., Pedrazzoni M., Marcato A., Vescovi P., Novarini A. Vertebral mineral content in diet-dependent and dietindependent hypercalciuria. J. Urol. 1991, 146: 1334–1338.

    CAS  PubMed  Google Scholar 

  19. Weisinger J.R., Alonzo E., Bellorin-Font E., Blasinc A.M., Rodriguez M.A., Paz-Martinez V., Martinis R. Possible role of cytokines on the bone mineral loss in idiopathic hypercalciuria. Kidney Int. 1996, 49: 244–250.

    Article  CAS  PubMed  Google Scholar 

  20. Ralston S.H., Ho L.P., Helfrich M., Grabowski P.S., Johnston P.W., Benjamin N. Nitric oxide: a cytokine induced regulator of bone resorption. J. Bone Miner. Res. 1995, 10: 1040–1049.

    Article  CAS  PubMed  Google Scholar 

  21. Greenwald R.A, Refkin B.R. Reactive oxygen species as potential mediators of osteoclast function. In: Rifkin B., Gay C. (Eds.), Biology and physiology of the osteoclast. CRC Press, Boca Raton, 1992, p. 316.

    Google Scholar 

  22. Ralston S.H., Grabowski P.S. Mechanisms of cytokine induced bone resorption: role of nitric oxide, cyclic guanosine monophosphate, and prostaglandins. Bone 1996, 19: 29–33.

    Article  CAS  PubMed  Google Scholar 

  23. Raisz L.G., Martin T.J. Prostaglandins in bone and mineral metabolism. In: Peck W.A. (Ed.), Bone and Mineral Research Annual. Excerpta Medica, Amsterdam, 1984, vol. 2, p. 286.

    Google Scholar 

  24. Roche C.H., Rodriguez-Iturbe B., Herrera J., Parra G. The influence of prostaglandins on urinary calcium excretion in idiopathic urolithiasis. J. Urol. 1988, 122: 421–426.

    Google Scholar 

  25. CaIò L., Cantaro S., Marchini F., Giannini S., Castrignano R., Gambaro G., Antonello A., Baggio B., D’Angelo A., Williams H., Borsatti A. Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis? Clin. Sci 1990, 78: 321–325.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dipartimento di Scienze Mediche e Chirurgiche, Divisione di Nefrologia, Università of Padova, Italy

    Lorenzo Calò M.D., S. Cantaro, A. D’Angelo & G. Crepaldi

  2. Clinica Medica I, Università of Padova, Italy

    S. Giannini & M. Nobile

  3. Laboratorio Centrale, Università of Padova, Italy

    P. Bonvicini & M. Plebani

  4. Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica 4°, University of Padova, Via Giustiniani 2, 35128, Padova, Italy

    A. Semplicini

  5. Azienda Ospedaliera di Padova, Italy

    Lorenzo Calò M.D., S. Giannini, P. Bonvicini, M. Nobile, S. Cantaro, M. Plebani, A. Semplicini, A. D’Angelo & G. Crepaldi

Authors
  1. Lorenzo Calò M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Giannini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Bonvicini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Nobile
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Cantaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Plebani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Semplicini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. D’Angelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Crepaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lorenzo Calò M.D..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calò, L., Giannini, S., Bonvicini, P. et al. Idiopathic hypercalciuria: O −2 NO relationship and altered bone metabolism. J Endocrinol Invest 23, 78–83 (2000). https://doi.org/10.1007/BF03343683

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03343683

Key-words

Search

Navigation