eMedicine Specialties > Physical Medicine and Rehabilitation > Spinal Cord Injury

Hypercalcemia and Spinal Cord Injury

Author: Teresa L Massagli, MD, Residency Director, Professor, Department of Rehabilitation Medicine and Pediatrics, University of Washington School of Medicine
Coauthor(s): Maria Regina L Reyes, MD, Acting Assistant Professor, Department of Rehabilitation Medicine, University of Washington; Medical Director, Inpatient Rehabilitation Medicine Service and Rehabilitation Consultation Service, University of Washington Medical Center
Contributor Information and Disclosures

Updated: Aug 19, 2008

Introduction

Background

The immobilization resulting from acute spinal cord injury (SCI) stimulates osteoclastic bone resorption. This process causes calcium loss from the bones and hypercalciuria. Hypercalcemia results when the efflux of calcium is massive or when the glomerular filtration rate of the kidneys is reduced.1

The onset of hypercalcemia usually is insidious. The patient may present with vague and varied symptoms beginning several weeks after SCI. Clinicians should suspect hypercalcemia in high-risk groups. If untreated, patients may develop dehydration, personality changes, calcium oxalate nephrolithiasis, and renal failure. Treatment is aimed at early mobilization, hydration, and restoration of the balance between calcium excretion and resorption.2,3

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Pathophysiology

Immobilization following SCI triggers an increase in osteoclastic bone resorption. The cascade of events that links the lack of mechanical forces on bone with enhanced resorption may involve altered piezoelectric effects in bone.4 The specific events are not understood completely. Muscle activity transmits a bone formation signal through the osteocyte. With immobilization, the mechanical stimulation for bone formation caused by muscle activity is reduced, leaving resorption unopposed. The bone resorption continues for up to 18 months after SCI, long after patients begin remobilization. The resorption ultimately results in osteoporosis, particularly of the appendicular skeleton.

The calcium released by bone resorption is excreted by the kidneys. Hypercalciuria develops within the first week after injury and continues for 6-18 months. The release of calcium suppresses production of parathyroid hormone (PTH) within several weeks of SCI. Reduced PTH is associated with increased serum phosphate concentrations and reduced synthesis of 1,25-dihydroxyvitamin D.5

If the rate of calcium resorption exceeds the capacity of urinary excretion, hypercalcemia results. This condition is most likely to occur in children, adolescents, and persons with impaired renal function. Hypercalcemia usually appears 4-8 weeks after SCI, but it can begin as early as 2 weeks or as late as 6 months after the injury.

Frequency

United States

Immobilization hypercalcemia occurs in approximately 10-23% of persons with SCI and affects adolescent and young adult males more commonly than it does other populations.6,7 This disorder is more common in patients with tetraplegia than it is in persons with paraplegia.8

Mortality/Morbidity

  • The degree of hypercalcemia associated with SCI has not been reported to reach the life-threatening levels that may occur in hypercalcemia of malignancy.
  • Acute hypercalcemia induces natriuresis (nephrogenic diabetes insipidus) and polyuria, possibly resulting in extracellular fluid contraction and dehydration.
  • Chronic hypercalcemia can reduce renal concentrating ability, further exacerbating polyuria and polydipsia. The disorder also causes urinary stones, nephrocalcinosis, and chronic renal failure.

Sex

Hypercalcemia is more common in males, possibly because of their greater bone mass.6

Age

Increased incidence in older children and adolescents probably is related to the rapid bone turnover that accompanies growth.6,9

Clinical

History

  • The onset of hypercalcemia is often insidious, and presenting symptoms can be vague. The clinician should maintain a high index of suspicion.
  • Patients with mild hypercalcemia may be asymptomatic. Symptomatic patients typically have serum calcium levels above 11.5-12 mg/dL.
  • Signs and symptoms of hypercalcemia include fatigue, lethargy, apathy, abdominal pain, constipation, anorexia, nausea, vomiting, polydipsia, polyuria, and dehydration.2 Patients also may exhibit behavioral changes, lassitude, lethargy, confusion, or an acute psychosis.
  • Severity of clinical symptoms is not associated with neurologic level.

Physical

No specific physical findings are associated with hypercalcemia of immobilization.

Causes

Immobilization after SCI triggers an increase in osteoclastic bone resorption. The cascade of events that link the lack of mechanical forces on bone with enhanced resorption may involve altered piezoelectric effects in bone.4 This mechanism is not understood completely.

More on Hypercalcemia and Spinal Cord Injury

Overview: Hypercalcemia and Spinal Cord Injury
Differential Diagnoses & Workup: Hypercalcemia and Spinal Cord Injury
Treatment & Medication: Hypercalcemia and Spinal Cord Injury
Follow-up: Hypercalcemia and Spinal Cord Injury
References
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References

  1. Moe SM. Disorders of calcium, phosphorus, and magnesium. Am J Kidney Dis. Jan 2005;45(1):213-8. [Medline].

  2. Maynard FM, Imai K. Immobilization hypercalcemia in spinal cord injury. Arch Phys Med Rehabil. Jan 1977;58(1):16-24. [Medline].

  3. Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care. Jun 2008;35(2):215-37. [Medline].

  4. Elias AN, Gwinup G. Immobilization osteoporosis in paraplegia. J Am Paraplegia Soc. Jul 1992;15(3):163-70. [Medline].

  5. Stewart AF, Adler M, Byers CM, et al. Calcium homeostasis in immobilization: an example of resorptive hypercalciuria. N Engl J Med. May 13 1982;306(19):1136-40. [Medline].

  6. Maynard FM. Immobilization hypercalcemia following spinal cord injury. Arch Phys Med Rehabil. Jan 1986;67(1):41-4. [Medline].

  7. Nand S, Goldschmidt JW. Hypercalcemia and hyperuricemia in young patients with spinal cord injury. Arch Phys Med Rehabil. 1976;57:553.

  8. Naftchi NE, Viau AT, Sell GH, Lowman EW. Mineral metabolism in spinal cord injury. Arch Phys Med Rehabil. Mar 1980;61(3):139-42. [Medline].

  9. Benjamin RW, Moats-Staats BM, Calikoglu's A, et al. Hypercalcemia in children. Pediatr Endocrinol Rev. Mar 2008;5(3):778-84. [Medline].

  10. Deftos LJ. Hypercalcemia in malignant and inflammatory diseases. Endocrinol Metab Clin North Am. Mar 2002;31(1):141-58. [Medline].

  11. Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. May 1 2003;67(9):1959-66. [Medline]. [Full Text].

  12. Tori JA, Hill LL. Hypercalcemia in children with spinal cord injury. Arch Phys Med Rehabil. Oct 1978;59(10):443-6. [Medline].

  13. Wick JY. Immobilization hypercalcemia in the elderly. Consult Pharm. Nov 2007;22(11):892-905. [Medline].

  14. Urivetzky M, Kessaris D, Smith AD. Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis. J Urol. May 1992;147(5):1215-8. [Medline].

  15. Gilchrist NL, Frampton CM, Acland RH, et al. Alendronate prevents bone loss in patients with acute spinal cord injury: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. Apr 2007;92(4):1385-90. [Medline]. [Full Text].

  16. Valverde P. Pharmacotherapies to manage bone loss-associated diseases: a quest for the perfect benefit-to-risk ratio. Curr Med Chem. 2008;15(3):284-304. [Medline].

  17. Meythaler JM, Tuel SM, Cross LL. Successful treatment of immobilization hypercalcemia using calcitonin and etidronate. Arch Phys Med Rehabil. Mar 1993;74(3):316-9. [Medline].

  18. Fitton A, McTavish D. Pamidronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs. Feb 1991;41(2):289-318. [Medline].

  19. Gucalp R, Ritch P, Wiernik PH, et al. Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia. J Clin Oncol. Jan 1992;10(1):134-42. [Medline].

  20. Machado CE, Flombaum CD. Safety of pamidronate in patients with renal failure and hypercalcemia. Clin Nephrol. Mar 1996;45(3):175-9. [Medline].

  21. Massagli TL, Cardenas DD. Immobilization hypercalcemia treatment with pamidronate disodium after spinal cord injury. Arch Phys Med Rehabil. Sep 1999;80(9):998-1000. [Medline].

  22. Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. Jan 15 2001;19(2):558-67. [Medline].

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Further Reading

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Keywords

hypercalcemia, spinal cord injury, SCI, osteoclastic bone resorption, immobilization hypercalcemia, calcium loss, hypercalciuria, calcium oxalate nephrolithiasis, renal failure, parathyroid hormone, natriuresis, nephrogenic diabetes insipidus, polyuria, extracellular fluid contraction, polydipsia, urinary stones, nephrocalcinosis, immobilization after spinal cord injury

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Contributor Information and Disclosures

Author

Teresa L Massagli, MD, Residency Director, Professor, Department of Rehabilitation Medicine and Pediatrics, University of Washington School of Medicine
Teresa L Massagli, MD is a member of the following medical societies: American Academy of Pediatrics, American Academy of Physical Medicine and Rehabilitation, and Association of Academic Physiatrists
Disclosure: Nothing to disclose.

Coauthor(s)

Maria Regina L Reyes, MD, Acting Assistant Professor, Department of Rehabilitation Medicine, University of Washington; Medical Director, Inpatient Rehabilitation Medicine Service and Rehabilitation Consultation Service, University of Washington Medical Center
Maria Regina L Reyes, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Spinal Injury Association, Association of Academic Physiatrists, and Washington State Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Patrick J Potter, BSc, MD, FRCP(C), Associate Professor, Physical Medicine and Rehabilitation, The University of Western Ontario; Consulting Staff, Department of Physical Medicine and Rehabilitation, St Joseph's Health Care Centre
Patrick J Potter, BSc, MD, FRCP(C) is a member of the following medical societies: American Paraplegia Society, Canadian Association of Physical Medicine and Rehabilitation, Canadian Medical Association, College of Physicians and Surgeons of Ontario, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kat Kolaski, MD, Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine
Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.

CME Editor

Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center
Disclosure: Nothing to disclose.

Chief Editor

Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers, Phoenix
Denise I Campagnolo, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers
Disclosure: Teva Neuroscience Honoraria Speaking and teaching; Serono-Pfizer Honoraria Speaking and teaching

 
 
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