Determination of the Impact of Functional Instability of Parathyroid Hormone and the Calcium-Phosphorus Ratio as Risk Factors during Osteoarthritic Disorders using Receiver Operating Characteristic Curves

  • Apurba Ganguly Founder and Head Researcher, OPTM Research Institute, 145 Rashbehari Avenue, Kolkata – 700029, India
Keywords: Osteoarthritic disorders, Diagnostic protocol, Calcium-phosphorus ratio, Parathyroid hormone, Degenerative changes, Receiver operating characteristics


Backgrounds: The disease risk factor prediction with calcium-phosphorus ratio (CPR) and/or parathyroid hormone (PTH) levels are suitable biomarkers. The aim of the present study was to investigate the functional instability of these biomarkers in the blood on the risk of osteoarthritic disorder (OAD) by using receiver operating characteristic (ROC) curves. Methods: Separate evaluations were performed for subjects 132 with OAD and 109 without OAD symptoms using questionnaires, standardized physical and radiographic examinations, and risk factor identification (hypoparathyroidism, hypocalcaemia and hyperphosphatemia diseases). The blood levels of PTH, calcium, and phosphorus were measured by using appropriate kits. ROC curve and logistic regression analyses were performed for the PTH and CPR levels. Results: The area under the ROC curve (AUC), 95% CI for the AUC, for the OAD compared with the non-OAD cohorts were 0.985, 0.969-1.000, and P<0.001 for the PTH analysis and 0.579, 0.506-0.652, and P<0.05 for the CPR analysis. In the OAD cohort, the AUC and the PTH risk were higher for men than for women; AUC=1.000 for men, and AUC=0.977 for women, with both AUC values highly significant (P<0.001). The CPR risk was higher for men (AUC=0.614, 95% CI=0.483-0.746, P=0.079) than for women (AUC=0.516, 95% CI=0.419-0.613, P=0.736) but was not statistically significant in either sex. Conclusion: A functional instability risk that is higher in male than female OAD cohorts causes lower PTH and CPR levels during OADs, which can be considered one of the OAD diagnostic protocols besides radiological images.


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1. Norman, J. Your Parathyroid Glands. Endocrineweb, 2010. Available from:
2. OpenStax. Bone Tissue and the Skeletal System. In: Anatomy and Physiology, OpenStax CNX. Chapter 6, 2016. Available from:[email protected]
3. Chambers TJ. The cellular basis of bone resorption. Clin. Orthop. Relat. Res. 1980;151:283-293.
4. Rodan GA, Martin TJ. The role of osteoblasts in hormonal control of bone resorption. Calcif. Tissue Int. 1981;33:349-351.
5. Fuller K, Owens JM, Chambers TJ. Induction of osteoclast formation by parathyroid hormone depends on an action on stromal cells. J. Endocrinol. 1998;158:341-350.
6. Lee S. Endogenous parathyroid hormone and knee osteoarthritis: a cross-sectional study. Int J Rheum Dis. 2016;19(3):248-254.
7. Mabey T, Honsawek S. Role of vitamin D in osteoarthritis: Molecular, cellular, and clinical perspectives. Int. J. Endocrinol. 2015. Available from:
8. Li H, Zeng C, Wei J, Yang T, Gao S-G, Li Y-S, et al. Serum calcium concentration is inversely associated with radiographic knee osteoarthritis A cross-sectional study. Medicine. 2016;95(6):e2838. DOI: 10.1097/MD.0000000000002838.
9. Pereira D, Lima RPA, de Lima RT, Goncalves MdaC, de Morais LC, Franceschini CC, et al. Association between obesity and calcium: phosphorus ratio in the habitual diets of adults in a city of Northeastern Brazil: An epidemiological study. Nutr. J. 2013;12:90. DOI: 10.1186/1475-2891-12-90.
10. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study. Am. J. Kidney. Dis. 1998;31:607-617.
11. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: Results of the study to evaluate early kidney disease. Kidney Int. 2007;71:31-38.
12. Ganguly A. Assessment of relationship between calcium-phosphorus ratio and parathyroid hormone levels in serum of osteoarthritic disordered patients: A diagnostic protocol. Pract. Lab. Med. 2017; Unpublished.
13. Walwadkar SD, Suryakar AN, Katkam RV, Kumbar KM, Ankush RD, Oxidative stress and calcium-phosphorus levels in rheumatoid arthritis. Indian J. Clin. Biochem. 2006;21(2): 134-137.
14. Cheesman KH, Slater TF. An introduction to free radical Biochemistry. Br. Med. Bull. 1993;49(3):481-493.
15. Bijlsma MD, Jacobs JW, Hormonal preservation of bone in rheumatoid arthritis. Rheum. Dis. Clin. North Am. 2000;26:897-910.
16. Otten JJ, Hellwig JP, Meyeers LD, Dietary reference intake: The essential guide to nutrient requirements. Washington DC, The National Academic Press, 2006.
17. Dhingra R, Sullivan LM, Fox CS, Wang TJ, D'Agostino Sr. RB, Gaziano M, et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch. Intern. Med. 2007;167:879-885.
18. Thomas L, Clinical Laboratory Diagnostics. 1st edition. Frankfurt: TH-Books Verlagsgesellschaft; 1998;241-247.
19. Endres DB, Rude RK. Mineral and bone metabolism, In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 3rd edition. Philadelphia: W.B Saunders Company; 1999;1395-1457.
20. Felson DT, Epidemiology of hip and knee osteoarthritis. Epidemiol. Rev. 1988;10:1-28.
21. Bijlsma JW, Berenbaum F, Lafeber FP, Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377:2115-2126.
22. Johnson VL, Hunter DJ. The epidemiology of osteoarthritis. Best Pract. Res. Clin. Rheumatol. 2014;28:5-15.
23. Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, et al. Osteoarthritis: New insights. Part 1: The disease and its risk factors. Ann. Intern. Med. 2000;133:635-646.
24. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. March, The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann. Rheum. Dis. 2014;73:1323-1330.
25. Ganguly A. Degenerative changes in lumbar region always lead to bilateral degenerative changes in knee-joints and vice-versa: Sensation of pain cannot only be the parameter of degeneration. Anat. Physol. 2015a;S4-005 doi:10/41722161-0940.S4-005.
26. Ganguly A. Degenerative changes in lumbar-region occur simultaneously with bilateral-osteoarthritic changes in knee-joints and vice versa: Normalization with topical application of phytoconstiuents by specialized techniques involving possible cartilage-regeneration. Int. J. Recent Sci. Res. 2015b;6(9):6331-6346.
27. 27 Ganguly A. Obtaining normal flexion and extension of knee joints on supine, prone and standing positions in osteoarthritis by topical phytotherapeutic treatment irrespective of age and sex. International Journal of Phytomedicine. 2015c;7(3):290-301.
28. Ganguly A. Tropical phytotherapeutic treatment for achieving knee symmetry in osteoarthritis - A sustainable approach. International Journal of Phytomedicine. 2014;6(4): 489-509.
29. Otterness IG, Swindell AC, Zimmerer RO, Poole AR, Ionescu M, Weiner E. An analysis of 14 molecular markers for monitoring osteoarthritis: segregation of the markers into clusters and distinguishing osteoarthritis at baseline. Osteoarthr. Carti. 2000;8:180-185.
30. Garnero P, Piperno M, Gineyts E, Christgau S, Delmas PD, Vignon E. Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations
with disease activity and joint damage. Ann. Rheum. Dis. 2001;60:619-626.
31. Liu J, Shikhman AR, Lotz MK, Wong C-H. Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis. Chem. Biol. 2001;8(7):701-711.
32. Parsons S, Alesci S, Feuerstein G, Wang J. Biomarkers in the development of novel disease-modifying therapies for osteoarthritis. Biomarkers Med. 2008;2(6):587-602.
33. Kaysen GA. Biochemistry and biomarkers of inflamed patients: Why look, What to assess. Clin. J. Am. Soc. Nephrol. 2009;4:S56-S63.
34. Dam EB, Loog M, Christiansen C, Byrjalsen I, Folkesson J, Nielsen M, et al. Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers. Arthritis Res. Ther. 2009;11(4):R115 doi: 10.1186/ar2774.
35. Long F, Cal X, Luo W, Chen L, Li K. Role of Aldolase in osteosarcoma progression and metastasis: In vitro and in vivo evidence. Oncol. Rep. 2014;32(5):2031-2037.
36. Gonen M. Analyzing receiver operating characteristic curves with SAS. Cary, NC, SAS Press, 2007.
37. Ghanem E, Antoci Jr. V, Pulido L, Joshi A, Hozack W, Parvizi J. The use of receiver operating characteristics analysis in determining erythrocyte sedimentation rate and C-reactive protein levels in diagnosing periprosthetic infection prior to revision total hip arthroplasty. Int. J. Infect. Dis. 2009;13:e444-e449.
38. Grund B, Sabin C. Analysis of biomarker data: logs, odds ratios and ROC curves. Curr. Opin. HIV AIDS. 2010;5(6):473-479.
39. Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008; 5(10):e203. doi:10.1371/journal.pmed.0050203.
40. Kay R, Little S. Transformations of the explanatory variables in the logistic regression model for binary data. Biometrika. 1987;74(3):495-501.
41. Cook RD, Weisberg S. Applied regression including computing and graphics. Chapter 22. New York: John Wiley and Sons; 1999;549-579
42. Harrell FE. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. New York: Springer, 2001.
43. Baker SG. Identifying combinations of cancer markers for further study as triggers of early intervention. Biometrics. 2000;56(4):1082-1087.
44. Xiong C., McKeel DWJ, Miller JP, Morris JC. Combining correlated diagnostic tests: application to europathologic diagnosis of Alzheimer's disease. Med. Decis. Making. 2004; 24(6):659-669.
45. Tsai CA, Chen JJ, Significance analysis of ROC indices for comparing diagnostic markers: applications to gene microarray data. J. BioPharma Stat. 2004;14(4):985-1003.
46. Mamtani MR, Thakre TP, Kalkonde MY, Kalkonde YV, Amin AP, Kulkarni H. Simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification. BMC Bioinformatics. 2006;7:442. doi:10.1186/1471-2105-7-442.
47. Michaylova V, Ilkova P. Photometric determination of micro amounts of calcium with arsenazo III. Anal. Chim. Acta. 1971;53:194-198.
48. Bauer PJ. Affinity and stoichiometry of calcium binding by arsenazo III. Anal. Biochem. 1981;110:61-72.
49. Raisz LG, Yajnik CH, Bockman RS, Bower BB. Comparison of commercially available parathyroid hormone immunoassay in the differential diagnosis of hypercalcemia due to primary hyperparathyroidism or malignancy. Ann. Intern. Med. 1979;91:739-740.
50. Mallette LE, The parathyroid polyhormones: New concepts in the spectrum of peptide hormone action. Endocrin. Rev. 1991;12:110-117.
51. Kruger L, Rosenblum S, Zaazra J, Wong J. Intact PTH is stable in unfrozen EDTA plasma for 48 hours prior to laboratory analysis. Clin. Chem. 1995;41(6): S47.
52. Norman J. Hypoparathyroidisms: Too Little Parathyroid Hormone Production. Endocrineweb, 2016. Available from:,
53. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie AG, Chertow GM, Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J. Am. Soc. Nephrol. 2004;15:2208-2218.
54. Johnson NP. Advantages to transforming the receiver operating characteristic (ROC) curve into likelihood ratio co-ordinates. Stat. Med. 23 (2004) 2257-2266.
55. Wisniewski H-G, Colón E, Liublinska V, Karia RJ, Stabler TV, Attur M. TSG-6 activity as a novel biomarker of progression in knee osteoarthritis. Osteoarthr. Cartil. 2014;22:235-241.
How to Cite
Ganguly A. Determination of the Impact of Functional Instability of Parathyroid Hormone and the Calcium-Phosphorus Ratio as Risk Factors during Osteoarthritic Disorders using Receiver Operating Characteristic Curves. Int Arch BioMed Clin Res [Internet]. 2017Dec.20 [cited 2020May28];3(4):47-2. Available from: