Best Dx/Best Rx: Osteoporosis

From: Subject: Best Dx/Best Rx: Osteoporosis Date: Wed, 3 Jun 2009 21:25:18 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_01B2_01C9E491.CB38ADD0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_01B2_01C9E491.CB38ADD0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx0306.htm Best Dx/Best Rx: Osteoporosis

Osteoporosis

Elizabeth Holt, M.D., Ph.D.
Silvio E. = Inzucchi,=20 M.D.
Yale University School of Medicine

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key=20 Clinical Features

Loss of bone mass, including loss of = trabecular bone=20 microarchitecture and connectivity and thinning of cortical bone, = leading to=20 increased risk of fracture=20
Bone mass density > 2.5 SDs below that of = normal,=20 young adult control population (dual x-ray absorptiometry [DXA] T = score <=20 -2.5)=20
Histomorphology
- Decreased cortex thickness=20
- Decreased number and size of trabeculae in = cancellous=20 bone=20
- Decreased trabecular connectivity=20
- Increased number of perforations in = trabecular=20 plates
Primary osteoporosis=20
- Occurs in the elderly, particularly women in = 6th=20 decade and older=20
- Bone fracture, pain, and spinal = deformity=20
- Both appendicular and axial skeleton are = involved,=20 with fractures occurring frequently in thoracic vertebrae = (compression=20 fractures), hip, and distal radius (Colles fracture) =
Secondary osteoporosis is associated with the=20 following:=20
- Endocrine disorders (hyperparathyroidism,=20 hyperthyroidism, Cushing syndrome, hypogonadism, growth hormone=20 deficiency)=20
- Systemic inflammatory disease (e.g., = rheumatoid=20 arthritis)=20
- Bone mineral and metabolic defects=20
- May be seen in younger women with = amenorrhea,=20 especially those with anorexia nervosa, and in athletes=20
- Renal, liver, and intestinal diseases (e.g., = malabsorption)=20
- Use of some medications, including=20 glucocorticoids=20
- Other chronic illnesses (e.g., multiple=20 myeloma)

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Differential = Diagnosis

Other Diagnoses = to Consider=20 for Low Bone Density or Nontraumatic Fractures=20

Metastatic cancer=20
Osteomalacia=20
Osteogenesis imperfecta=20
Paget disease

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Best=20 Tests

DXA of proximal femur, lumbar spine, or = nondominant=20 distal radius=20
- Positioning of patient may affect results,=20 particularly at the hip and wrist=20
- Degenerative disease or scoliosis in the = lumbar spine=20 can make the bones appear denser=20
- Comparison studies should be performed on = same=20 densitometer if possible
Plain radiographs=20
- Only able to identify significant = osteoporosis=20
- May be useful to assess for silent = fractures=20
- May help to assess for classical = roentgenographic=20 features of certain metabolic bone diseases, such as osteomalacia = and=20 hyperparathyroidism

Clinical=20 Pearls=20

Risk of fracture is not only predicted by = T-score;=20 relative contribution of other risk factors such as age (and others = below) is=20 significant=20
Once osteoporosis is diagnosed, consider = causes of=20 secondary bone loss (other than estrogen deficiency) using a = comprehensive=20 history and physical exam to exclude relevant diseases; this should be = followed by laboratory testing for any conditions suspected=20

Red Flags=20

Spontaneous high thoracic or cervical = fractures with=20 minimal trauma should raise suspicions of malignancy=20
Risk of death within 1 yr of hip fracture is=20 significantly increased

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Best=20 Therapy

Modifiable Risk Factors=20

Smoking cessation=20
Moderation of alcohol consumption=20
Weight-bearing physical activity=20
Physical therapy evaluation to improve safety = and=20 stability=20
Home safety evaluations to prevent = falls=20
Review medication lists for frail elderly = patients to=20 eliminate medications that may cause dizziness or sedation=20

Drug Treatment for = Osteoporosis=20

Consider drug therapy for postmenopausal women = with DXA=20 T-score < =962.5 in the absence of risk factors for fracture and = for=20 postmenopausal women with DXA T-score < =961.5 in the presence of = risk=20 factors for fracture=20
Most important risk factors for fracture =
- Personal history of fracture after age 40 = yr=20
- Family history of osteoporosis in a = first-degree=20 relative
- Current cigarette smoking=20
- Low body weight, < 127 lb, regardless of=20 height
Calcium supplementation=20
- May help prevent further bone loss but not = effective=20 alone as therapy=20
- Should be used in conjunction with other = therapeutic=20 agents below=20
- In elderly patients, those on proton pump = inhibitors=20 or H₂ receptor blockers, and patients with pernicious = anemia,=20 calcium citrate may be better absorbed than calcium carbonate =
- Take calcium carbonate with food=20
- Take calcium citrate on empty stomach =
  - Dose: 1,000=961,500 mg/day=20
  - Cost/mo: $3
Vitamin D supplementation
- May help prevent further bone loss but not = effective=20 alone as therapy=20
- Vitamin D deficiency is associated with = increased risk=20 of falls=20
- Should be used in conjunction with other = therapeutic=20 agents (see below)
- Excessive intake may result in = hypercalcemia=20
- Patients taking medications (e.g., = phenytoin) that=20 increase vitamin D metabolism may need higher doses=20
  - Dose: 400=96800 IU/day=20
  - Cost/mo: $3
Bisphosphonates: antiresorptive agents
- Preferred agents for most patients with=20 osteoporosis=20
- Alendronate and risedronate (but not = ibandronate) have=20 been demonstrated to reduce both vertebral and nonvertebral = fractures=20
- Risk reduction for fracture is ~ = 35=9650%=20
- Contraindicated in patients with esophageal=20 dysmotility, stricture or varices, or active esophagitis/gastritis;=20 creatinine clearance must be above 35 ml/min=20
- Use with caution in patients with history of = esophagitis or gastroesophageal reflux disease=20
- Osteonecrosis of the jaw is a rare side = effect of=20 agents in this class=20
- Use with caution in women of childbearing = age
- Concern for adynamic bone: consider a 1- to = 2-yr drug=20 holiday after 5=9610 yr of oral bisphosphonate therapy
- Take first thing in the morning on empty = stomach with=20 full glass of water, remain upright, and do not consume other = drinks,=20 medications or food for 30 min=20
  - Alendronate
    - FDA-approved for hip fracture = prevention=20
    - Dose
      - Prevention: 35 mg p.o. once a wk =
      - Treatment: 70 mg p.o. once a wk for = osteoporosis=20 defined by BMD or fractures
    - Cost/mo: $69 (35 mg/wk); $78 (70 = mg/wk)=20
  - Risedronate
    - Not FDA-approved for hip fracture=20 prevention=20
    - Dose: 35 mg p.o. once a wk for = prevention or=20 treatment=20
    - Cost/mo: $68
  - Ibandronate
    - Not FDA-approved for hip fracture=20 prevention=20
    - Dose=20
      - Prevention and treatment: 150 mg = once/mo=20
    - Cost/mo: $76 =
Raloxifene: antiresorptive agent
- Not FDA-approved for hip fracture = prevention=20
- Selective estrogen receptor modulator (SERM) =
- Does not increase risk of breast cancer =
- Increased risk of thromboembolic = disease=20
- May cause/worsen hot flashes=20
- Reduces vertebral fractures but not = nonvertebral=20 fractures=20
- Usually used only if bisphosphonates not = tolerated or=20 contraindicated
  - Dose: 60 mg/day p.o.=20
  - Cost/mo: $85
Calcitonin: antiresorptive agent
- Reduces vertebral fractures but not = nonvertebral=20 fractures=20
- May provide pain relief in those with acute = vertebral=20 fractures=20
- Tachyphylaxis is a concern=20
- Usually used if other agents not tolerated = or=20 contraindicated
  - Dose: 200 IU/day intranasally
  - Cost/mo: $93
Estrogen: antiresorptive hormone=20
- Should be limited to those who require = relief of=20 menopausal symptoms=20
- Reduces both vertebral and nonvertebral=20 fractures=20
- Risk reduction for fracture is ~ 50%
- ERT should be accompanied by a comprehensive = screening=20 program consisting of regular lipid profiles, breast examinations,=20 mammography, and gynecologic assessments=20
- Contraindicated in those with history of = breast or=20 uterine cancer or thrombotic disorders=20
- Increases the incidence of breast cancer,=20 cardiovascular events, and stroke=20
- In women with an intact uterus, must be used = in=20 conjunction with progestational agent=20
- When used without progestins, also increases = the risk=20 of uterine cancer=20
  - Dose: 0.625 mg oral conjugated = estrogen/day or 0.1=20 mg 17 b-estradiol transdermal for days = 1 to=20 21=20
  - Cost/mo: oral, $32; transdermal, $86=20
Teriparatide (recombinant human PTH [1-34]): = anabolic=20 agent
- Reduces both vertebral and nonvertebral=20 fractures=20
- Has not been shown to prevent hip = fracture=20
- Black box warning from FDA because of = association with=20 osteosarcoma in rats=20
- Use for patients with the following:=20
  - Severe osteoporosis
  - History of vertebral fracture, T-score = =963.0 or=20 below, or age > 69 yr=20
  - Fracture or unexplained bone loss in = patients on=20 antiresorptive therapy=20
  - Intolerance of oral bisphosphonate = therapy=20
- Side effects include flushing, = hypercalcemia, and=20 hypercalciuria=20
- Serum calcium and 24-hr urine calcium levels = must be=20 monitored and calcium intake adjusted as needed
- Can be administered for no longer than 2 = yr=20
- Contraindicated in patients with active = malignancy,=20 hypercalcemia, Paget disease, history of irradiation to the = skeleton,=20 sarcoma, or malignancy involving bone=20
- Simultaneous use with antiresorptive agents = appears to=20 reduce its efficacy=20
- When bisphosphonate therapy follows = treatment with=20 teriparatide, the effects of teriparatide are enhanced and = maintained=20
  - Dose: 20 mg = S.Q./day=20
  - Cost/mo: $587 =

Clinical Pearls=20

Reduce fracture risk through the following = measures:=20
- Maintaining body weight=20
- Weight-bearing physical exercise=20
- Avoiding drugs that may cause sedation or = falls=20
- Treating impaired vision=20
- Hip protectors have been shown to be = effective in some=20 clinical trials
Osteoporosis in men is idiopathic in about = half of=20 cases; identifiable causes include the following:
- Hypogonadism=20
- Alcohol abuse=20
- Liver or intestinal disease =
Men benefit from calcium repletion, adequate = vitamin D=20 intake, appropriate exercise regimen, and antiresorptive agents, if=20 applicable

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Best = References

Body JJ, et al: J Clin Endocrinol Metab 87:4528, = 2002 [PMID=20 12364430]

Liberman UA, et al: N Engl J Med 333:1437, 1995 = [PMID=20 7477143]

Maricic M, et al: Arch Intern Med 162:1140, 2002 = [PMID=20 12020184]

McClung MR, et al: N Engl J Med 344:333, 2001 = [PMID=20 11172164]

NIH Consensus Panel: JAMA 285:785, 2001 [PMID=20 11176917]

Women's Health Initiative Investigators: JAMA = 288:321, 2002=20

July=20 2006

=A9 = 2006 WebMD,=20 Inc.=20