Intended for healthcare professionals

Rapid response to:


Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials

BMJ 2006; 333 doi: (Published 12 October 2006) Cite this as: BMJ 2006;333:775

Rapid Response:

The Changing Face of Hypercalcaemia

Over the last decade, the number of subjects diagnosed with
hypercalcaemia has increased exponentially (5-fold) mainly because of
laboratory automation and the introduction of plasma calcium determination
in routine biochemical screening.1,2 Recent advances in our
understanding of the pathophyisological changes in metabolic bone diseases
(MBD) have resulted in increasing numbers of patients being treated with
calcium and/or vitamin D supplements.3,4 Hypercalcaemia is a serious and
not infrequent complication of malignant disease. Correct interpretation
and recognition of the underlying cause has a major impact on the
management and morbidity of these patients.5 We undertake this hospital-
based survey to determine the causes and the biochemical profile in
hypercalcaemic patients.

118286 calcium requests were received from 39360 patients between April 2003
and April 2004. Out of 118286 requests, the proportion with
hypercalcaemia (Adjusted Calcium >2.60 mmol/L) was 10% (11702). The
largest proportions were from subjects with chronic kidney disease (CKD),
renal transplant (RTX) and osteoporosis(OP), 53%, 21% and 6.7%,
respectively. The next commonest causes of hypercalcaemia from this survey
were malignancy followed by primary hyperparathyroidism (1o HPT), 11% and
3.5%, respectively. A characteristic pattern of hyperchloraemia and
normal anion-gap was revealed in patients with 1o HPT. The likelihood of
having 1o HPT was 3-5 fold higher in patients with Cl/PO4 ratio >129
compared to malignancy.

This survey has revealed that hypercalcaemia is a common metabolic
problem; iatrogenic factor is the commonest cause and need to be ruled out
before embarking on expensive investigations. Combining Cl/PO4 ratio to
the bone profile may help in the differentiation between 1oHPT and


1. Fisken RA, Heath DA, Bold AM. Hypercalcaemia--a hospital survey. Q J
Med. 1980;49:405-18

2. Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary
hyperparathyroidism. N Engl J Med. 2004; 22:1746-51.

3. Muhammedi MA, Piraino B, Rault R, Johnston JR, Puschett JB. Iatrogenic
hypercalcemia in hemodialysis patients.Clin Nephrol. 1991;36:258-61.

4. Kato Y, Sato K, Sata A, Omori K, Nakajima K, Tokinaga K, Obara T,
Takano K.
Hypercalcemia induced by excessive intake of calcium supplement

5. Burkhardt E, Kistler HJ. [Hypercalcemia in hospitalized patients.
Diagnostic and prognostic aspects] Schweiz Med Wochenschr.

Competing interests:
None declared

Competing interests: No competing interests

27 September 2006
Ali I Al-bahrani
Senior Registrar
William DFraser , Eilleen Manning, L Ranganth, Trevor Hine
Dept Clinical Biochemistry, Royal Liverpool University Hospital, Duncan Building, Liverpool L69 3GA