REVIEW
Secondary Causes of Osteoporosis

https://doi.org/10.4065/77.5.453Get rights and content

Secondary causes of bone loss are not often considered in patients who are diagnosed as having osteoporosis. In some studies, 20% to 30% of postmenopausal women and more than 50% of men with osteoporosis have a secondary cause. There are numerous causes of secondary bone loss, including adverse effects of drug therapy, endocrine disorders, eating disorders, immobilization, marrow-related disorders, disorders of the gastrointestinal or biliary tract, renal disease, and cancer. Patients who have undergone organ transplantation are also at increased risk for osteoporosis. In many cases, the adverse effects of osteoporosis are reversible with appropriate intervention. Because of the many treatment options that are now available for patients with osteoporosis and the tremendous advances that have been made in understanding the pathogenesis and diagnosis of the condition, it is important that medical disorders are recognized and appropriate interventions are undertaken. This article provides the framework for understanding causes of bone loss and approaches to their management.

Section snippets

ESTIMATES OF THE INCIDENCE OF SECONDARY OSTEOPOROSIS

One of the challenges encountered in the discussion of secondary osteoporosis is understanding the problems of the disorder in the general population. Cost concerns have limited use of thorough work-ups to rule out all possible secondary causes, or studies may reflect experiences from subspecialty clinics or tertiary medical care centers where inherent bias may be present.

A small proportion of women with low trauma fractures have osteomalacia, and in men with femoral fractures, osteomalacia is

Glucocorticoids

Decalcification of the skeleton was recognized as a clinical feature of Cushing disease as early as 1932. Glucocorticoid excess results in diffuse bone loss and may affect trabecular bone more than cortical bone. Bone loss is due to suppression of osteoblast function, inhibition of intestinal calcium absorption leading to secondary hyperparathyroidism, and increased osteoclast-mediated bone resorption. Bone loss is also promoted by direct stimulation of renal excretion of calcium by

MISCELLANEOUS CAUSES OF SECONDARY OSTEOPOROSIS Eating Disorders

Anorexia nervosa and bulimia affect 5% to 10% of women.70 Onset may be at any time from adolescence through the fourth decade of life. These eating disorders are resistant to treatment and chronic in nature, which results in significant morbidity and mortality.

Anorexia nervosa has been associated with osteoporosis. There are several metabolic disorders associated with anorexia nervosa that may adversely affect the skeleton. These include estrogen deficiency, endogenous cortisol excess, reduced

DISEASES OF THE PANCREAS Pancreatic Insufficiency

Clinically significant bone disease in patients with pancreatic insufficiency due to cystic fibrosis or total pancreatectomy is not unusual. In children or young adults with cystic fibrosis, reduced bone density has been found and may be confounded by variables such as glucocorticoid use and hypogonadism.103,104 Clinical features include diabetes mellitus and steatorrhea. Steatorrhea probably has the most impact on vitamin D and calcium malabsorption. In a patient with bone disease secondary to

DISEASES OF THE LIVER

Liver diseases may cause bone disease because of the inability of the liver to convert vitamin D to 25-hydroxy-vitamin D. The role of vitamin D depends on hepatically produced vitamin D transport proteins, albumin, and vitamin D binding protein. The development of bone disease also depends on the transport of vitamin D metabolites to the target tissues, the degree to which enterohepatic circulation of vitamin D as metabolites contributes to the maintenance of bone, and the role of bile in

TRANSPLANTATION OSTEOPOROSIS

Organ transplantation has become an effective therapy for end-stage renal, hepatic, cardiac, and pulmonary disease.112 One-year patient survival is excellent, averaging 98% for living donor kidney, 87% for liver, and 85% for cardiac transplant recipients.113 Many patients now live for more than 10 years. Unfortunately, many transplant patients demonstrate a propensity to fracture, which greatly aggravates their quality of life. The pathogenesis of transplantation osteoporosis is incompletely

TARGETING INTERVENTIONS OF AN ASYMPTOMATIC PATIENT POPULATION

There is much controversy regarding the best work-up for patients who have been diagnosed as having osteoporosis based on BMD. The problem with attempting to apply strict diagnostic criteria regarding who may have a secondary or reversible cause of osteoporosis is that few data exist to provide adequate guidance. Most of the information that has been gathered has either been from subspecialty clinics, which would have an inherent bias (such as a rheumatology clinic where glucocorticoid

REFERENCES (148)

  • CJ Rosen et al.

    Emerging anabolic treatment for osteoporosis

    Rheum Dis Clin North Am

    (2001)
  • N Udagawa et al.

    Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand

    Bone

    (1999)
  • GK Reddy et al.

    The biomechanical integrity of bone in experimental diabetes

    Diabetes Res Clin Pract

    (2001)
  • S Nielsen

    Epidemiology and mortality of eating disorders

    Psychiatr Clin North Am

    (2001)
  • PC Rambaut et al.

    Skeletal changes during space flight

    Lancet

    (1985)
  • CL Donaldson et al.

    Effect of prolonged bed rest on bone mineral

    Metabolism

    (1970)
  • BL Pear

    Skeletal manifestations of the lymphomas and leukemias

    Semin Roentgenol

    (1974)
  • MJ Pais

    Disease states affecting both liver and bone

    Radiol Clin North Am

    (1980)
  • RL Eddy

    Metabolic bone disease after gastrectomy

    Am J Med

    (1971)
  • D Meyer et al.

    Osteoporosis in a North American adult population with celiac disease

    Am J Gastroenterol

    (2001)
  • S Mora et al.

    Effect of gluten-free diet on bone mineral content in growing patients with celiac disease

    Am J Clin Nutr

    (1993)
  • T Kemppainen et al.

    Bone recovery after a gluten-free diet: a 5-year follow-up study

    Bone

    (1999)
  • S Mora et al.

    Bone density and bone metabolism are normal after long-term gluten-free diet in young celiac patients

    Am J Gastroenterol

    (1999)
  • ST Haden et al.

    Calcidiol and PTH levels in women attending an osteoporosis program

    Calcif Tissue Int

    (1999)
  • P Peris et al.

    Aetiology and presenting symptoms in male osteoporosis

    Br J Rheumatol

    (1995)
  • GA Caplan et al.

    Pathogenesis of vertebral crush fractures in women

    J R Soc Med

    (1994)
  • N Kelepouris et al.

    Severe osteoporosis in men

    Ann Intern Med

    (1995)
  • TP Van Staa et al.

    Use of oral corticosteroids and risk of fractures

    J Bone Miner Res

    (2000)
  • E Canalis et al.

    Glucocorticoid-induced osteoporosis: summary of a workshop

    J Clin Endocrinol Metab

    (2001)
  • R McKenzie et al.

    Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo controlled trial

    J Rheumatol

    (2000)
  • E Israel et al.

    Effects of inhaled glucocorticoids on bone density in premenopausal women

    N Engl J Med

    (2001)
  • GA Michel et al.

    Fractures in rheumatoid arthritis: an evaluation of associated risk factors

    J Rheumatol

    (1993)
  • M Centrella et al.

    Differential actions of prostaglandins in separate cell populations from fetal rat bone

    Endocrinology

    (1994)
  • TL McCarthy et al.

    Alternate signaling pathways selectively regulate binding of insulin-like growth factor I and II on fetal rat bone cells

    J Cell Biochem

    (1998)
  • RS Weinstein et al.

    Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone

    J Clin Invest

    (1998)
  • RS Weinstein et al.

    Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip

    J Clin Endocrinol Metab

    (2000)
  • American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis

    Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update

    Arthritis Rheum

    (2001)
  • BP Lukert

    Glucocorticoid-induced osteoporosis

  • S Gonnelli et al.

    Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients

    Calcif Tissue Int

    (1997)
  • JD Adachi et al.

    Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis

    N Engl J Med

    (1997)
  • JD Adachi et al.

    Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial

    Arthritis Rheum

    (2001)
  • S Cohen et al.

    Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study

    Arthritis Rheum

    (1999)
  • CE Dent et al.

    Osteomalacia with long-term anticonvulsant therapy in epilepsy

    Br Med J

    (1970)
  • J Hunter et al.

    Altered calcium metabolism in epileptic children on anticonvulsants

    Br Med J

    (1971)
  • G Pylypchuk et al.

    Calcium metabolism in adult outpatients with epilepsy receiving long-term anticonvulsant therapy

    Can Med Assoc J

    (1978)
  • B Ashworth et al.

    Evidence of osteomalacia in an outpatient group of adult epileptics

    Epilepsia

    (1977)
  • RT Matheson et al.

    Absorption and biotransformation of cholecalciferol in drug-induced osteomalacia

    J Clin Pharmacol

    (1976)
  • TJ Hahn et al.

    Phenobarbital-induced alterations in vitamin D metabolism

    J Clin Invest

    (1972)
  • H Gough et al.

    A comparative study of the relative influence of different anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in out-patients with epilepsy

    Q J Med

    (1986)
  • DD Bikle

    Drug-induced osteomalacia

    • Cited by (228)

    • The role and mechanism of RNA-binding proteins in bone metabolism and osteoporosis

      2024, Ageing Research Reviews

    • Roles of the Siglec family in bone and bone homeostasis

      2023, Biomedicine and Pharmacotherapy

    • Osteoporosis

      2023, Medical Clinics of North America

    • Nox4 promotes osteoblast differentiation through TGF-beta signal pathway

      2022, Free Radical Biology and Medicine

    • Biodistribution and toxicity of antimicrobial ionic silver (Ag<sup>+</sup>) and silver nanoparticle (AgNP<sup>+</sup>) species after oral exposure, in Sprague-Dawley rats

      2022, Food and Chemical Toxicology

    • What traditional, complementary, and integrative medicine recommendations exist across osteoporosis clinical practice guidelines? A systematic review and quality assessment

      2022, Integrative Medicine Research
    View all citing articles on Scopus
    View full text
    Copyright © 2002 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.