Skip to main content

Advertisement

SpringerLink
Log in

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy

  • Clinical Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Summary

In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n=13), 45 mg (n=9), and 90 mg (n=13) in an attempt to see what factors influenced the response of serum calcium to pamidronate.

The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into “good” and “poor” responders depending on whether a normal serum calcium was obtained.

Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r=0.45, P=0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean±SEM): 65.0±9.4 nmol/liter GF (poor responders) versus 29.6±6.3 (good responders), P=0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r=-0.41, P=0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF±0.09 (poor responders) versus 0.76 mmol/liter GF±0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response. A significant negative correlation was evident between NcAMP and TmPO4 (r=-0.35, P=0.003), however, no significant correlation was evident between NcAMP and TmCa or TmPO4 and TmCa.

These results suggest that in a hypercalcemic patient where evidence exists for the presence in circulation of a factor with PTH-like activity (i.e., NcAMP is elevated or TmPO4 is low) the response of serum calcium to pamidronate is less good. NcAMP would appear to be a useful predictor of the response of serum calcium, whereas TmPO4 is less discriminating.

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. Mundy GR, Martin TJ (1982) The hypercalcaemia of malignancy: pathogenesis and management. Metabolism 131:1247–1277

    Google Scholar 

  2. Ralston SH, Gallacher SJ, Patel U, Campbell J, Boyle IT (1990) Cancer-associated hypercalcaemia: morbidity and mortality. Clinical experience in 126 treated patients. Ann Int Med 112: 499–504

    Google Scholar 

  3. Ralston SH, Gardner MD, Dryburgh FJ, Jenkins AS, Cowan RA, Boyle IT (1985) Comparison of aminohydroxypropylidene diphosphonate, mithramycin, and corticosteroids/calcitonin in treatment of cancer-associated hypercalcaemia. Lancet 2:907–910

    Google Scholar 

  4. Ralston SH, Gallacher SJ, Patel U, Dryburgh FJ, Fraser WD, Cowan RA, Boyle IT (1989) Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia. Lancet 2:1180–1182

    Google Scholar 

  5. Gurney H, Kefford R, Stuart-Harris R (1989) Renal phosphate threshold and response to pamidronate in humoral hypercalcaemia of malignancy. Lancet 2:241–244

    Google Scholar 

  6. Thiebaud D, Jaeger P, Jacquet AF, Burckhardt P (1988) Doseresponse in the treatment of hypercalcaemia of malignancy by a single infusion of the bisphosphonate AHPrBP. J Clin Oncol 6:762–768

    Google Scholar 

  7. Gallacher SJ, Ralston SH, Fraser WD, Dryburgh FJ, Cowan RA, Logue FC, Boyle IT (1991) A comparison of low versus high dose pamidronate in cancer-associated hypercalcaemia. Bone Miner 15:249–256

    Google Scholar 

  8. Ralston SH, Alzaid AA, Gallacher SJ, Gardner MD, Cowan RA, Boyle IT (1988) Clinical experience with aminohydroxypropylidene bisphosphonate (APD) in the management of cancer-associated hypercalcaemia. Q J Med (new series) 69:825–834

    Google Scholar 

  9. Ralston SH, Alzaid AA, Gardner MD, Boyle IT (1986) Treatment of cancer-associated hypercalcaemia with combined aminohydroxypropylidene bisphosphonate (APD) and calcitonin. Br Med J 292:1549–1550

    Google Scholar 

  10. Gardner MD, Dryburgh FJ, Fyffe JA, Jenkins AS (1981) Predictive value of derived calcium figures based on the measurement of ionised calcium. Ann Clin Biochem 18:106–109

    Google Scholar 

  11. O'Reilly D StJ, Fraser WD, Penney MD et al. (1986) Arginine infusion blocks the action of parathyroid hormone but not arginine vasopressin on the renal tubule in man. J Endocrinol 111: 501–506

    Google Scholar 

  12. Broadus AE, Mahaffey JE, Bartter FO, Neer RM (1977) Nephrogenous cyclic adenosine monophosphate as a parathyroid function test. J Clin Invest 60:771–783

    Google Scholar 

  13. Walton RJ, Bijvoet OLM (1975) Nomogram for the derivation of renal threshold phosphate concentration. Lancet 2:309–310

    Google Scholar 

  14. Beastall GH, McKellar N, Boyle IT, et al. (1983) Pre-operative localisation of parathyroid tumours using neck vein catheterisation and radioimmunoassay of parathyroid hormone: the Glasgow experience. Scot Med J 28:146–152

    Google Scholar 

  15. Logue FC, Perry B, Chapman RS, Milne I, James K, Beastall GH (1991) A two-site immunoradiometric assay for PTH (1–84) using N and C terminal specific monoclonal antibodies. Ann Clin Biochem 28:160–166

    Google Scholar 

  16. Ralston S, Fogelman I, Gardner M, Boyle IT (1982) Hypercalcaemia and metastatic bone disease: is there a causal link? Lancet 2:903–905

    Google Scholar 

  17. Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE (1980) Biochemical evaluation of patients with cancer-associated hypercalcaemia: evidence for humoral and nonhumoral groups. N Engl J Med 303:1377–1383

    Google Scholar 

  18. Mosely JM, Kubota M, Diefenbach-Jagger H, et al. (1987) Parathyroid hormone-related protein purified from a human lung cancer line. Proc Natl Acad Sci USA 84:5048–5052

    Google Scholar 

  19. Suva LJ, Winslow GA, Wettenhall REH, et al. (1987) A parathyroid hormone-related protein implicated in malignant hypercalcaemia: cloning and expression. Science 237:893–896

    Google Scholar 

  20. Sabatini M, Boyce B, Aufdemorte T, Bonewald L, Mundy GR (1988) Infusions of human interleukins 1 alpha and 1 beta cause hypercalcaemia in normal mice. Proc Natl Acad Sci USA 85:5235–5239

    Google Scholar 

  21. Suzuki K, Yamada S (1991) Ascites sarcoma 180, an animal model of humoral hypercalcaemia of malignancy, produces of factor(s) exhibiting potent bone-resorbing activity without any parathyroid hormone-like activity. Bone Miner 14:1–13

    Google Scholar 

  22. Martin TJ (1990) Properties of parathyroid hormone-related protein and its role in malignant hypercalcaemia. Q J Med (new series) 76:771–786

    Google Scholar 

  23. Hughes DE, McDonald BR, Russell RGG, Gowen M (1989) Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow. J Clin Invest 83: 1930–1935

    Google Scholar 

  24. Nordin BEC, Horsman A, Aaron J (1976) In: Nordin BEC (ed) Calcium, phosphate and magnesium metabolism. Churchill Livingstone Edinburgh, p 475

    Google Scholar 

  25. Judson I, Booth F, Gore M, McElwain T (1990) Chronic high dose pamidronate in refractory malignant hypercalcaemia (letter). Lancet 335:802

    Google Scholar 

  26. Morton RA, Friefield J, Haperin F (1990) Dose of bisphosphonate for hypercalcaemia of malignancy (letter). Lancet 335: 1469–1470

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Department of Medicine, Glasgow Royal Infirmary, Queen Elizabeth Building, G31 2ER, Glasgow, UK

    Stephen J. Gallacher, Iain T. Boyle & Stuart H. Ralston

  2. Institute of Biochemistry, Glasgow Royal Infirmary, Queen Elizabeth Building, G31 2ER, Glasgow, UK

    Fraser C. Logue, Frances J. Dryburgh & Robert A. Cowan

  3. University Department of Clinical Chemistry, Royal Liverpool Hospital, Liverpool, UK

    William D. Fraser

Authors
  1. Stephen J. Gallacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William D. Fraser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fraser C. Logue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frances J. Dryburgh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert A. Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Iain T. Boyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stuart H. Ralston
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gallacher, S.J., Fraser, W.D., Logue, F.C. et al. Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy. Calcif Tissue Int 51, 419–423 (1992). https://doi.org/10.1007/BF00296674

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00296674

Key words

Search

Navigation