Last updated: November 16, 2014
ICD-9 Codes: Generalized, 733.0; postmenopausal, 733.1; idiopathic 733.02; drug induced 733.09; dis-use 733.03; osteopenia 733.90
ICD-10 Codes: M80 – M82; Age related osteoporosis without fracture M81.0
Definition: Osteoporosis is a reduction in bone mass with microarchitectural deterioration leading to bone fragility and fracture.
Etiology: Many causes have been identified (Table A) including excess glucocorticoids (Cushing’s or iatrogenic), deficiencies of sex steroids in men and women, lack of gravitational force (immobilization or space flight), chronic active inflammation, or nutritional deficiencies (calcium, vitamin D) which may result from dietary lack or malabsorption. Estrogen deficiency mediates enhanced bone loss through production of cytokines including IL-1.
Pathology: Bone mineral and organic phases are structurally normal and present in normal proportions. The primary defect is in bone remodeling where there is an imbalance between bone resorption and formation. Factors that influence bone remodeling (e.g, estrogen deficiency, steroid use, immobilization, etc.) can increase osteoclast activity, uncoupling the bone remodeling process and affecting the total quantity of bone. Histologic findings show reduction in trabecular thickness. Cytokines that have been associated with bone remodeling include: IL-1, IL-6, IL-11, TGF, RANKL, and TNF.
Demographics: Over 10 million Americans are affected by osteoporosis, and 1.5 million osteoporotic fractures occur annually. Postmenopausal women represent the largest patient group. Men older than age 60 may show decreasing bone density, although increased fracture risk does not appear until after age 70. The risk of vertebral compression fracture and hip fracture in postmenopausal white women is nearly 20%. Black individuals tend to have greater bone density and are thus at a much lower risk of osteoporotic fractures. Patients of all ages who are treated with chronic glucocorticoids have accelerated bone loss.
|Table A. Risk Factors for Development of Osteoporosis|
Hypogonadal (both genders)
Small skeletal mass (Weight < 127 lbs.)
Lifestyle habits: tobacco, alcohol, lack of exercise, malnutrition
Medications: glucocorticoids, anticonvulsants, lithium, aromatase inhibitors, thyroid preparations, heparin, cyclosporine
Comorbid conditions: hyperparathyroidism, hyperthyroidism, diabetes mellitus, malabsorption syndromes, Cushing syndrome, rheumatoid arthritis, multiple myeloma, alcoholism
Cardinal Findings: At the outset, osteoporosis is clinically silent. In later stages, fracture may occur in the vertebral bones, with resulting wedge-shaped deformities that can cause radiating pain and contribute to formation of an exaggerated kyphosis, known as the dowager ’s hump. Other sites at risk of fracture include the forearm (Colles fracture) and the hip. Fractures in osteoporotic ribs may be induced by coughing and can cause considerable pain. Cortical bone stress fractures may occur in the lower extremities or feet.
Uncommon Manifestations: Loss of height, a protruberant abdomen, and decreased pulmonary capacity may be signs of osteoporosis. Vertebral fractures can rarely cause spinal cord compromise. Although bisphosphonate use has been reported to increase the risk of atrial fibrillation or esophageal cancer, FDA analysis has failed to establish any substantive risk for atrial fibrillation or esophageal cancer with chronic bisphosphonate use.
Complications: Osteonecrosis of the jaw (ONJ) is a rare event in OP patients receiving bisphosphonates with an adverse event risk ranging from 1:4000 to 1:250,000. The associate between oral bisphosphonates and ONJ is a remote one with no clear relationship between the risk and duration of therapy. Another rare event is the unusual occurrence of femoral shaft fracturs with “atypical” features suggesting a brittle bone-type fracture. This has primarily been reported in patients receiving long-term antiresorptive therapy (average duration 7 years). Two studies suggest that risk increases with long-term bisphosphonate therapy, with a risk of 5-100 fractures per 100,000 patients exposed for 5-10 years. For those with a low to modest fracture risk, interruption of treatment for 1-3 years (“drug holiday”) is appropriate after 3-5 years of chronic therapy.
Diagnostic Tests: Osteoporosis may be suspected based on routine conventional radiography; note that about 25-50% of loss in bone mass must occur to detect osteopenia on x-rays. While radiographs are an insensitive measure of bone density, occult fractures may be detected. Bone densitometry (e.g., DEXA scan) measurements are diagnostic (see p. 66). DEXA should include two sites: the hip and lumbar spine. DEXA with vertebral fracture assessments (VFA) enhances the ability to detect previous fractures. Indications for bone density testing are listed in Table B. Standard lab tests that are important in assessing patients for secondary causes of osteoporosis include: CBC, CMP, TSH, alkaline phosphatase, 25- OH vitamin D, measurement/estimated 24 hour urinary calcium. Consideration can be made for evaluating the ESR, intact PTH, SPEP/UPEP based on clinical suspicion. Men with osteoporosis should have testosterone levels checked. Biochemical markers of bone turnover are available but not routinely done.
|Table B. ISCD Position Statement: Indications for Bone Density Testing|
|All women > 65 years old
All postmenopausal women <65 yrs. with 1 or more risk factors (low body weight, prior fracture, high risk medication use, disease associated with osteoporosis)
Men > 70 years old
Men <70 y.o with 1 or more risk factors
Previous fragility fracture
Osteopenia or vertebral abnormalities documented on radiographs
Anyone being treated, to monitor treatment effect
Anyone not receiving therapy where evidence of bone loss would lead to treatment
Keys to Diagnosis: An early diagnosis can be made (before fractures occur) if an individual in the at-risk population (Table A) is identified and routinely assessed by bone densitometry or radiographic studies.
Differential Diagnosis: Osteoporotic fractures should be distinguished from pathologic fractures and their underlying abnormalities (i.e., bony metastases). Primary hyperparathyroidism causes accelerated bone loss in primarily cortical bone, especially the hip. Osteomalacia may be associated with low levels of 25- hydroxyvitamin D and phosphate and appear like osteoporosis on bone density. Bone biopsy may be required for definitive diagnosis of osteomalacia. Heritable disorders of connective tissue, including Marfan’s and Ehlers-Danlos syndromes, are often associated with osteoporosis.
Therapy: The primary goal of therapy should be prevention of fractures.
—General measures: Lifestyle adjustments should include cessation of tobacco use and of excessive intake of alcohol. Weight-bearing exercise is recommended. Frail and elderly patients with high fracture risk should have a living situation that does not require use of stairs, and ambulation aids should be used if necessary.
—Drugs: Calcium (1,000–1,500 mg/day) and vitamin D supplementation are recommended for all. In postmenopausal women, long-term hormone replacement with conjugated estrogens (with or without progesterone) is effective but has been associated with other unacceptable (cardiovascular, breast cancer) risks. Other options include the use of raloxifene (selective estrogen receptor modulator), bisphosphonates (i.e., alendronate, risedronate, zolendronate, ibandronate), teriparatide (synthetic parathyroid hormone), and denosumab (RANKL inhibitor. The recent release of daily subcutaneous injections of teriparatide (synthetic parathyroid hormone) has added to the arsenal against osteoporosis. The use of sodium fluoride is controversial. Combinations of these therapies are being studied, data have not proven any benefits over monotherapy. The use of strontium and calcitonin is controversial. Although, calcitonin may have analgesic properties, and has been used in the treatment of painful fractures.
|Table C. 2010 ACR guidelines on prevention and management of glucocorticoid induced osteoporosis (GIO)|
|1. Use the lowest effective steroid dose for the shortest duration possible
2. Counsel on lifestyle modifications (weight bearing activities, tobacco cessation, avoid alcohol > 2 drinks/day)
3. Assess fall risks
4. Obtain baseline (and consider annual measurements) of height, DEXA, and 25-OH vitamin D level
5. Assess for prevalent fragility fractures
6. Start calcium intake 1200-1500 mg/day, with vitamin D 800-1000 IU daily
7. Treat with osteoporosis medications if postmenopausal female (or male > 50 yrs at risk for fracture) receiving glucocorticosteroid >3 months >7.5 mg/day*:
*Any individuals with previous fragility fractures on glucocorticoids >1 month should be considered for therapy as above.
Surgery: Surgery is rarely required except to stabilize fractures. Early detection of vertebral collapse may be managed with vertebroplasty (high pressure infusion of cement into collapsed vertebra) or kyphoplasty (vertebral height restored using an intravertebral balloon followed by cement) to relieve pain and restore vertebral morphology. Bone biopsy is occasionally required to confirm that other conditions (osteomalacia, hyperparathyroidism, Paget disease, metastatic disease) are not present.
Prognosis: Fractures (especially hip fractures) in elderly patients are associated with significant morbidity and mortality. Improved awareness and a wide range of available treatments for osteoporosis may significantly change the course of this disease.
Brown SA, Rosen CJ. Osteoporosis. Med Clin North Am 2003;87:1039–1063. PMID:14621330
Garfin SR. New technologies in spine: kyphoplasty and vertebroplasty for the treatment of painful osteoporotic compression fractures. Spine 2001;26:1511–1515. PMID:11462078
Bray VJ. Osteoporosis Screening Guideline. ISCS.org
Saag KG. Glucocorticoid-induced osteoporosis. Endocrinol Metab Clin North Am 2003; 32:135–157. PMID:12699296
Grossman JM, Gordon R, Ranganath VK, Deal C, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 2010; 62):1515-26. PMID:20662044
McClung MR. The safety of osteoporosis medications. ACR Drug Safety Quarterly 2013; 4(3): 1,4,8