|Year : 2007 | Volume
| Issue : 1 | Page : 17-19
An unusual case of hypercalcaemic osteomalacia: Role of a novel calcimimetic agent
YJ Anupama, B Ravishankar, KS Babu, HS Ballal
Manipal Institute of Nephrology and Urology, Manipal Hospital, Bangalore, India
H S Ballal
Manipal Institute of Nephrology and Urology, Manipal Hospital, 98, Rustom Bagh, Airport Road, Bangalore - 560 017
Source of Support: None, Conflict of Interest: None
Rickets is commonly seen in childhood and is characterized by hypocalcaemia, hypovitaminosis D, and skeletal deformities. Alhough rare in adults, it can cause devastating bone disease and severe secondary hyperparathyroidism. We report the case of a young adult with vitamin D deficient osteomalacia, severe hyperparathyroidism, and hypercalcemia with multiple fractures that resulted in prolonged immobilization. This case report highlights the approach to be adopted, the problems in management, and the benefits that accrued from the use of a novel calcimimetic agent.
Keywords: Calcimimetics, hypercalcemia, hyperparathyroidism, vitamin D deficiency
|How to cite this article:|
Anupama Y J, Ravishankar B, Babu K S, Ballal H S. An unusual case of hypercalcaemic osteomalacia: Role of a novel calcimimetic agent. Indian J Nephrol 2007;17:17-9
|How to cite this URL:|
Anupama Y J, Ravishankar B, Babu K S, Ballal H S. An unusual case of hypercalcaemic osteomalacia: Role of a novel calcimimetic agent. Indian J Nephrol [serial online] 2007 [cited 2020 Sep 23];17:17-9. Available from: http://www.indianjnephrol.org/text.asp?2007/17/1/17/35016
| ~ Introduction|| |
Vitamin D deficiency leads to hypocalcemia and secondary hyperparathyroidism. A sustained deficiency causes rickets in the growing skeleton and osteomalacia in the adult skeleton. We report the case of a young adult with vitamin D deficient osteomalacia, hypercalcemia, and severe hyperparathyroidism who was treated with a calcimimetic agent.
| ~ Case Report|| |
A 19-yr old college student presented with complaints of severe pain and muscular weakness in both the upper and lower limbs for a period of 3 months. The pain was diffuse and was worse in the lower limbs; the muscular weakness was predominantly in the lower limbs. He could walk with support for a few months but subsequently became wheelchair-bound. He was born to nonconsanguineous parents and had delayed motor milestones. There was no family history of a similar illness. He had frontal bossing during early childhood, which regressed with dietary interventions. He also had knock-knees for which he had not received any specific treatment. On examination, his height was 150 cm; he could not be weighed. He had severe tenderness over both the upper and lower limbs and all the limb movements were extremely painful. The muscle power was grade 2/5 in the upper limbs and grade 1/5 in the lower limbs. His systemic examination was unremarkable.
Investigations revealed hemoglobin 12.4g/dl, total leukocyte count 7800/mm 3 , and platelet count 3.4 lakhs/mm 3 ; urine pH 7.0, specific gravity 1020, with traces of protein; BUN 9.0 mg/dl, creatinine 0.5 mg/dl, sodium 144 mEq/l, potassium 3.7 mEq/l, chloride 108 mEq/l, bicarbonate 19.1 mmol/l, calcium 11.2 mg/dl, phosphate 1.9 mg/dl, alkaline phosphatase 2503 IU/l, plasma parathormone (PTH) 2267 pg/ml and serum 25(OH)D 3 1.5 ng/ml (normal >10 ng/ml). His 24-h urine amino acid excretion was normal and the fractional excretion of phosphorus was 31%. X-rays of the long bones and spine showed diffuse osteopenia, X-ray pelvis showed deformity of femoral heads and evidence of Looser's zones, X-ray of chest revealed multiple rib fractures, and X-ray of the wrist joints showed widened epiphyses with the fuzzy appearance suggestive of osteomalacia. Ultrasonography of the neck was unremarkable, and a Sestamibi scan of the parathyroid glands showed no adenoma.
A diagnosis of vitamin D deficient osteomalacia with tertiary hyperparathyroidism was made. He could not be given vitamin D and calcium because of the hypercalcemia and was, therefore, started on cinacalcet, a calcimimetic agent which reduces PTH without increasing serum calcium. After 4 weeks the serum PTH and calcium were 686 pg/ml and 9.3 mg/dl, respectively, and he was started on oral vitamin D. At 3 months, the muscle power, serum PTH, calcium, and alkaline phosphatase values improved significantly [Table - 1]. Repeat X-rays of wrists showed signs of healing [Figure - 1]. He was advised to continue cinacalcet 60 mg/day along with oral calcium and vitamin D.
| ~ Discussion|| |
Osteomalacia in adults is most often caused by vitamin D deficiency or resistance to vitamin D. It can occur in the elderly, in nursing home inmates, in patients on anticonvulsant therapy, and in vegetarians; in some countries, it may be due to the types of clothing worn, lack of exposure to sunlight, and poor vitamin D intake.
Our patient had signs of rickets (frontal bossing and knock-knees) during early childhood, later presenting with severe osteomalacia and severe hyperparathyroidism at the age of 19 years. Narchi et al .  have reported symptomatic rickets in 21 adolescents who had inadequate vitamin D intake along with poor exposure to sunlight at the time when they had increased growth velocity. Thomas et al .  studied vitamin D deficiency in medical inpatients and reported a prevalence of 57% and severe vitamin D deficiency (< 8 ng/ml) in 22%. Vitamin D dependent rickets (VDDR) and the acquired form of hypophosphatemic osteomalacia (oncogenic) are two other conditions that present with similar clinical and radiological findings as vitamin D deficient osteomalacia. They can be easily differentiated by estimating the plasma vitamin D levels. In VDDR, the vitamin D level is either normal or high, whereas in patients with hypophosphatemic osteomalacia, the vitamin D, calcium and PTH levels are normal [Table - 2].
This young adult presented with severe osteomalacia (severe proximal myopathy, pathological fractures, and grossly elevated alkaline phosphatase and PTH) and initially suspected to have primary hyperparathyroidism since he had severe hypophosphatemia with hypercalcemia. However the very high alkaline phosphatase, the radiological findings, and the very low vitamin D levels suggested longstanding vitamin D deficiency. Even though it is rare to see such a severe vitamin D deficiency in adults it is possible, especially in growing children in whom the dietary intake is inadequate, with no supplementation and little exposure to sunlight.
Chronic vitamin D deficiency is a well-recognized risk factor for severe secondary hyperparathyroidism. Ghazali et al .  demonstrated an inverse relationship between serum PTH and vitamin D levels. Our patient had very low vitamin D levels and the serum PTH level was about 30 times higher than normal. The patient had hypercalcemia with normal renal function, which could possibly have resulted because of severe tertiary hyperparathyroidism which has been described in chronic, untreated vitamin D deficiency. In addition, severe bone resorption as a result of the hyperparathyroid state and prolonged immobilization could have contributed to his hypercalcemia.
The hypercalcemia in this patient may have been caused by tertiary hyperparathyroidism, which does occur in chronic vitamin D deficiency.
In this particular patient, the presence of hypercalcemia precluded the use of vitamin D and calcium till PTH and calcium levels were lowered. In such cases, vitamin D analogs (doxercalciferol and paricalcitol) are useful to suppress PTH without increasing the calcium. Although vitamin D analogs can suppress PTH levels without affecting serum calcium and phosphorus, some elevation in their levels has been described with these compounds. Calcimimetics are a newer class of drugs that suppress PTH without elevating serum calcium and phosphorus levels. They act on calcium-sensing receptors in the parathyroid gland and suppress PTH secretion by increasing the threshold to circulating calcium. These drugs are being increasingly used in secondary hyperparathyroidism in patients with chronic kidney disease (CKD). These agents have been found to be very effective in suppressing PTH in patients on hemodialysis.  Block et al .  demonstrated suppression of plasma PTH to less than 250 pg/ml in 43% of patients and a 30% reduction in another 60% of the patients who received cinacalcet. However, there are no reports of the use of cinacalcet in patients who have vitamin D deficiency with hyperparathyroidism.
Our young patient had chronic vitamin D deficiency with a few signs of rickets in early childhood but later presented with devastating bone disease that made him bedridden for many months. The severe hyperparathyroid state could have contributed to the severe myopathy and the pathological fractures. The use of cinacalcet dramatically reduced the PTH and alleviated the need for surgical parathyroidectomy.
To conclude, chronic vitamin D deficiency presenting as osteomalacia is relatively rare in adults, and an unrecognized severe hyperparathyroid state can exist before the patient presents with symptomatic bone disease. The usual treatment of chronic vitamin D deficiency is supplementation with vitamin D and calcium. However, this is a unique case, where osteomalacia was associated with hypercalcemia and severe hyperparathyroidism, necessitating the use of a calcimimetic agent to reduce the PTH and calcium before vitamin D and calcium could be started. He had significant clinical, biochemical, and radiological improvement within a short period of time after starting cinacalcet therapy.
| ~ References|| |
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|3.||Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353-73. [PUBMED] |
|4.||Ghazali A, Fardellone P, Pruna A, Atik A, Achard JM, Oprisiu R, et al . Is low plasma 25(OH) Vit D, a major risk factor for hyperparathyroidism and Looser's zones independent of calcitriol? Kidney Int 1999;55:2169-77. [PUBMED] [FULLTEXT]|
|5.||Lindberg JS, Culleton B, Wong G, Borah MF, Clark RV, Shapiro WB, et al . Cinacalcet HCL, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis. J Am Soc Nephrol 2005;16:800-7. [PUBMED] [FULLTEXT]|
|6.||Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG, et al . Cinacalcet for secondary hyperparathyroidism in patients receiving haemodialysis. N Engl J Med 2004;350:1516-25. [PUBMED] [FULLTEXT]|
[Figure - 1]
[Table - 1], [Table - 2]