Skip to main content

Advertisement

Log in

Impact of urinary calcium excretion on kidney, bone, and cardiovascular systems in patients with bone biopsy proven osteoporosis: a longitudinal long-term follow-up study

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

The impact of urine calcium on kidney, bone, and cardiovascular systems in osteoporosis is not well-known. In this 7-year-follow-up study, high urine calcium did not affect kidney function but increased risk of kidney stones, while low urine calcium increased cardiovascular diseases. Maintaining normal urine calcium is beneficial for bone health.

Purpose

Hypercalciuria is common in patients with osteoporosis. However, the long-term effect of urinary calcium excretion (UCaE) on patients’ health is not well-examined. The current study aims to assess the impact of UCaE on kidney, bone, and cardiovascular outcomes in patients with bone biopsy proven osteoporosis.

Methods

Longitudinal study of all patients with osteoporosis who underwent bone biopsy and 24-h urine collection between 2008 and 2015 in the University of Kentucky. DXA scans, serum markers, kidney function, and cardiovascular events were recorded until last clinic visit in 2021. Exclusion criteria were secondary osteoporosis or conditions that might substantially impact UCaE. The significant results in univariate analysis were confirmed in multi-variable regression models involving clinically important covariates that might impact patients’ outcomes.

Results

Study included 230 patients with mean follow-up of 7.2 ± 2.9 years. The mean age was 61 years, and the mean eGFR at baseline was 85 ± 19 ml/min/1.73 m2. Low bone turnover (LBT) was present in 57% and high bone turnover (HBT) in 43% of patients. Hypercalciuria was found in one-third of patients with no difference between LTB and HTB. UCaE correlated positively with eGFR but did not affect the rate of eGFR decline over time. Higher UCaE predicted kidney stones development. We observed U-shaped effect of UCaE on bone health. Hypercalciuria predicted loss of BMD at all sites, but also hypocalciuria was associated with higher loss in total hip BMD. Upper limb fractures were the most observed fractures, and their incidence was higher in patients with hyper- or hypo-calciuria. Lower UCaE independently predicted development of major adverse cardiac events (MACE) and cardiovascular disease (CVD).

Conclusion

UCaE correlated with eGFR but it did not affect the change of eGFR over time. Patients with normal UCaE had lower incidence of upper limb fractures and less reduction in BMD. Low UCaE predicted MACE and CVD.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Glaser DL, Kaplan FS (1997) Osteoporosis: definition and clinical presentation. Spine 22(24):12S–16S

    Article  CAS  PubMed  Google Scholar 

  2. Malluche HH et al (2012) Differences in bone quality in low- and high-turnover renal osteodystrophy. J Am Soc Nephrol 23(3):525–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sakhaee K et al (2011) Nephrolithiasis-associated bone disease: pathogenesis and treatment options. Kidney international 79(4):393–403

    Article  CAS  PubMed  Google Scholar 

  4. Heller H et al (2007) Reduced bone formation and relatively increased bone resorption in absorptive hypercalciuria. Kidney international 71(8):808–815

    Article  CAS  PubMed  Google Scholar 

  5. Bordier P et al (1977) On the pathogenesis of so-called idiopathic hypercalciuria. Am J Med 63(3):398–409

    Article  CAS  PubMed  Google Scholar 

  6. El-Husseini A et al (2017) Urinary calcium excretion and bone turnover in osteoporotic patients. Clinical Nephrology 88(5):239

    Article  CAS  PubMed  Google Scholar 

  7. Kurz P et al (1994) Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. Kidney international 46(3):855–861

    Article  CAS  PubMed  Google Scholar 

  8. Godron A et al (2012) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: phenotype-genotype correlation and outcome in 32 patients with CLDN16 or CLDN19 mutations. Clin J Am Soc Nephrol 7(5):801–809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Thakker RV (2000) Pathogenesis of Dent's disease and related syndromes of X-linked nephrolithiasis. Kidney Int 57(3):787–793

    Article  CAS  PubMed  Google Scholar 

  10. Wrong O, Norden A, Feest T (1994) Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. QJM: An International Journal of Medicine 87(8):473–493

    CAS  PubMed  Google Scholar 

  11. Taylor JM et al (2017) Urinary calcium excretion and risk of chronic kidney disease in the general population. Kidney Int Rep 2(3):366–379

    Article  PubMed  Google Scholar 

  12. Duan S et al (2021) Association of urinary calcium and phosphorus excretion with renal disease progression in type 2 diabetes. Diabetes Res Clin Pract 178:108981

    Article  CAS  PubMed  Google Scholar 

  13. Alhava EM, Juuti M, Karjalainen P (1976) Bone mineral density in patients with urolithiasis. A preliminary report. Scand J Urol Nephrol 10(2):154–156

    Article  CAS  PubMed  Google Scholar 

  14. Malluche HH et al (1980) Abnormal bone histology in idiopathic hypercalciuria. J Clin Endocrinol Metab 50(4):654–658

    Article  CAS  PubMed  Google Scholar 

  15. Asplin JR et al (2006) Urine calcium excretion predicts bone loss in idiopathic hypercalciuria. Kidney Int 70(8):1463–1467

    Article  CAS  PubMed  Google Scholar 

  16. Kobayashi E et al (2002) Association between urinary calcium excretion level and mortality in inhabitants of the Jinzu River basin area of Japan. Biol Trace Elem Res 89(2):145–153

    Article  CAS  PubMed  Google Scholar 

  17. Liu J et al (2022) Determinants and outcomes associated with urinary calcium excretion in chronic kidney disease. J Clin Endocrinol Metab 107(1):e281–e292

    Article  PubMed  Google Scholar 

  18. Welles CC et al (2012) Urine calcium excretion, cardiovascular events, and mortality in outpatients with stable coronary artery disease (from the Heart and Soul study). Am J Cardiol 110(12):1729–1734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Corder, C.J., et al., 24-hour urine collection, in StatPearls. 2022, StatPearls Publishing Copyright 2022, StatPearls Publishing LLC.: Treasure Island (FL).

  20. Inker LA et al (2021) New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med 385(19):1737–1749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Martínez García M et al (2019) A comparison of induced effects on urinary calcium by thiazides and different dietary salt doses: implications in clinical practice. Nefrologia (Engl Ed) 39(1):73–79

    Article  PubMed  Google Scholar 

  22. Leslie SW, Sajjad H, Hypercalciuria, in StatPearls. (2022) StatPearls Publishing Copyright © 2022. Treasure Island (FL), StatPearls Publishing LLC

    Google Scholar 

  23. Pak CY et al (2011) Defining hypercalciuria in nephrolithiasis. Kidney Int 80(7):777–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Krolewski AS et al (2014) Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care 37(1):226–234

    Article  CAS  PubMed  Google Scholar 

  25. Cauley JA et al (2004) Bone mineral density and prevalent vertebral fractures in men and women. Osteoporos Int 15(1):32–37

    Article  PubMed  Google Scholar 

  26. Hui SL, Slemenda CW, Johnston CC Jr (1988) Age and bone mass as predictors of fracture in a prospective study. J Clin Invest 81(6):1804–1809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Malluche HH et al (2014) Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol 9(7):1254–1262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schousboe JT et al (2013) Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. J Clin Densitom 16(4):455–466

    Article  PubMed  Google Scholar 

  29. Alswat KA (2017) Gender disparities in osteoporosis. J Clin Med Res 9(5):382–387

    Article  PubMed  PubMed Central  Google Scholar 

  30. Humadi A, Alhadithi RH, Alkudiari SI (2010) Validity of the DEXA diagnosis of involutional osteoporosis in patients with femoral neck fractures. Indian J Orthop 44(1):73–78

    Article  PubMed  PubMed Central  Google Scholar 

  31. Shoback D et al (2020) Pharmacological management of osteoporosis in postmenopausal women: an endocrine society guideline update. J Clin Endocrinol Metab 105(3):587–594

    Article  Google Scholar 

  32. Eller-Vainicher C et al (2013) Prevalence of subclinical contributors to low bone mineral density and/or fragility fracture. Eur J Endocrinol 169(2):225–237

    Article  CAS  PubMed  Google Scholar 

  33. Romagnoli E et al (2011) Secondary osteoporosis in men and women: clinical challenge of an unresolved issue. J Rheumatol 38(8):1671–1679

    Article  PubMed  Google Scholar 

  34. Rathod A et al (2015) Association of urinary calcium excretion with serum calcium and vitamin D levels. Clin J Am Soc Nephrol 10(3):452–462

    Article  CAS  PubMed  Google Scholar 

  35. Curhan GC et al (2001) Twenty-four-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int 59(6):2290–2298

    Article  CAS  PubMed  Google Scholar 

  36. Hill KM et al (2013) Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int 83(5):959–966

    Article  CAS  PubMed  Google Scholar 

  37. Spiegel DM, Brady K (2012) Calcium balance in normal individuals and in patients with chronic kidney disease on low-and high-calcium diets. Kidney international 81(11):1116–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Vallés PG, Batlle D (2018) Hypokalemic distal renal tubular acidosis. Adv Chronic Kidney Dis 25(4):303–320

    Article  PubMed  Google Scholar 

  39. Yamada H et al (2018) Association between urinary calcium excretion and estimated glomerular filtration rate decline in patients with type 2 diabetes mellitus: a retrospective single-center observational study. J Clin Med 7(7):171

    Article  PubMed  PubMed Central  Google Scholar 

  40. Han SG et al (2019) Kidney stones and risk of osteoporotic fracture in chronic kidney disease. Sci Rep 9(1):1929

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ganesan C et al (2021) Osteoporosis, fractures, and bone mineral density screening in veterans with kidney stone disease. J Bone Miner Res 36(5):872–878

    Article  CAS  PubMed  Google Scholar 

  42. Taylor EN et al (2016) Nephrolithiasis and risk of incident bone fracture. J Urol 195(5):1482–1486

    Article  PubMed  Google Scholar 

  43. Carbone LD et al (2015) Urinary tract stones and osteoporosis: findings from the women’s health initiative. J Bone Miner Res 30(11):2096–2102

    Article  PubMed  Google Scholar 

  44. Asplin JR et al (2003) Bone mineral density and urine calcium excretion among subjects with and without nephrolithiasis. Kidney Int 63(2):662–669

    Article  CAS  PubMed  Google Scholar 

  45. Vezzoli G et al (2005) Urinary calcium is a determinant of bone mineral density in elderly men participating in the InCHIANTI study. Kidney Int 67(5):2006–2014

    Article  PubMed  Google Scholar 

  46. Rull MA et al (2015) The importance of urinary calcium in postmenopausal women with osteoporotic fracture. Can Urol Assoc J 9(3-4):E183–E186

    Article  PubMed  PubMed Central  Google Scholar 

  47. Xie JX et al (1992) The relationship between urinary cations obtained from the INTERSALT study and cerebrovascular mortality. J Hum Hypertens 6(1):17–21

    CAS  PubMed  Google Scholar 

  48. Vannucci L et al (2018) Calcium intake in bone health: a focus on calcium-rich mineral waters. Nutrients 10(12):1930

    Article  PubMed  PubMed Central  Google Scholar 

  49. Elias RM, Moe S, Moysés RMA (2021) Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis. J Bras Nefrol 43(4):539–550

    Article  PubMed  Google Scholar 

Download references

Funding

Mohamed Abdalbary was supported by the International Society of Nephrology (ISN) fellowship during his participation in this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Abdalbary.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary materials 1:

Supplementary Table 1: Significant correlations between baseline UCaE and baseline results. Supplementary Table 2: Binary logistic regression for development of new kidney stones. Supplementary Table 3: Urinary laboratory parameters among patients with and without kidney stones.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdalbary, M., Chishti, E., Shakhashiro, M. et al. Impact of urinary calcium excretion on kidney, bone, and cardiovascular systems in patients with bone biopsy proven osteoporosis: a longitudinal long-term follow-up study. Osteoporos Int 34, 763–774 (2023). https://doi.org/10.1007/s00198-023-06686-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-023-06686-x

Keywords

Navigation