Osteopenia - Low bone mass

Osteoporosis - compromised bone strength predisposing a person to an increased risk of fracture

Kyphosis - Excessive outward curvature of the spine causing hunching of the back

Lordosis - Inward curvature of the spine

Osteoclasts - bone resorbing cells

Osteoblasts - bone-forming cells (B = Build)

Patho - Low bone mineral density, where bone resorption is > bone formation.  PTH can increase osteoclast and osteoblast activity, whereas estrogen and calcitonin will decrease bone resorption.

Etiology:

Post-Menopausal --> Caused by estrogen deficiency

Age-related --> Accelerated bone turnover, immature bone dominates

Secondary --> Caused by disease states or drug therapies

Causes:

Disease - Cushing's, Hyper-PTH, malabsorption, nutritional disorders, renal disease, rheumatoid arthritis, thyrotoxicosis

Drugs - Corticosteroids, anticonvulsants, excessive alcohol, thyroxine, heparin, MTX, GRH agents, aromatase inhibitors

General - Fractures can occur while bending, lifting, falling, or indepedent of any activity

Symptoms - Pain, immobility, emotional symptoms

Signs - Shortened stature, kyphosis, lordosis

Labs - Need to determine secondary cause

Diagnostics - Spine and hip bone-density measurement using DXA

- Fractures of vertebrae, femur, and distal radius

- Decreased QOL, increased morbidity and mortality, increased risk of subsequent fracture.

- History of fracture

- Family history of osteoporosis

- Caucasian race

- Advanced age

- Female gender

- Small stature

- Current cigarette smoking

- Low body weight

- Estrogen deficiency

- Low calcium intake

- Inadequate physical activity

- Alcoholism

- Central Dual-Energy X-Ray Absorptiometry, also known as Dexa

- Composed of T-scores and Z-scores

- T-score is BMD compared to that of a normal sex-matched 30 year old, and the actual score is the number of standard devs from the mean of the reference population

- Z-score is BMD compared to that of a sex and AGE matched reference

- All post-menopausal women <65 years of age with 1 or more risk factors

- All women age 65 and older or man 70 and older

- A man age 50-70 with 1 or more risk factors

- A woman or man after age 50 who has broken a bone

- A woman going through menopause with risk factors

- A woman on HRT for prolonged periods

Normal BMD --> -1 and above T-score, below average fracture risk

Osteopenia --> -1 to -2.5 T-score, above average fracture risk

Osteoporosis --> -2.5 and below T-score, high fracture risk.

Postmenopausal women and men age 50 and older with the following:

- Hip or vertebral fracture

- T-score <-2.5 at the femoral neck of spine after appropriate evaluation to exclude 2nd causes

- T-score between -1 and -2.5 with risk factors

**DEXA testing should be done every 1-2 years**

Preventative:  Increase peak bone mass, decrease rate of subsequent bone loss, prevent fractures

Osteoporosis treatment:  Stabilize bone mass, minimize bone loss, pain relief, prevent fractures, maintain patient's ability to function

- Calcium and Vitamin D supplementation, or foods high in both (dairy, OJ, fortified breads and cereal, spinach, soybeans, salmon, etc.)

- Avoid high intake of caffeine, protein, and phosphorous

- Smoking cessation

- Exercise including weight-bearing activities

- Fall prevention

Adults < 50 - 1,000mg Calcium, 400-800IU Vitamin D

Adults > 50 - 1200mg Calcium, 800-1,000IU Vitamin D

- Calcium Carbonate contains most elemental Calcium but requires acidic environment for absorption

- Calcium citrate is better tolerated for patients with GI distress, doesn't require acidic absorption

**Body can only absorb 400-500mg at a time**

- 1st line for prevention and treatment of osteoporosis

- Bone resorption inhibitors, decrease osteoclast maturation, number, recruitment, bone adhesion, lifespan; incorporated into bone, long T 1/2

- Reduce fractures and increase BMD

- Take in morning, 30 min. before breakfast, full glass of water, empty stomach, don't lie down for 30 minutes

- AE's include esophageal irritation, musculoskeletal complaints, and osteonecrosis of the jaw (ONJ)

Alendronate - 35mg/week prevention, 70mg/week treatment

Risendronate - Prevention or treatment is 35mg/week or 150mg/month; steroid-induced disease is 5mg qd.

Ibandronate (Boniva) - Prevention or Treatment is 2.5mg qd or 150mg/month, 3mg IV q3months, infused over 30 seconds

Zoledronic Acid (Reclast) - 5mg IV q12 months; infused over no less than 15 min.

Risk Factors:  invasive dental procedures, poor oral hygiene, glucocorticoid use radiation or chemo, history of DM or cancer

- Highest risk of ONJ is with high dose IV bisphosphonates for > 2 years, with oral meds benefits outweight risk.

- All wounds from dental surgery should be healed prior to bisphosphonate therapy

- Long term therapy is safe with bisphosphonates, although BMD did gradually decline.  If patient responds well in first 5 years, perhaps consider a drug holiday

- Recombinant human parathyroid hormone

- Acts as an anabolic agent, stimulating bone formation

- 1st line if patient has T-score of < -3.5

- 20mcg SC injection daily for max 2 years

- Blackbox is risk of osteosarcoma

- Side effects include N/V, dizziness, leg cramps, not for patients with inc. risk of bone tumors.

- Administer first dose with patient sitting b/c of orthostatic HTN, inject SC into thigh or abdomen over 5 seconds

- Refrigerate before and after use

- Pens can be used for up to 28 days after 1st injection

- Mixed estrogen agonist/antagonist, dose of 60mg daily

- Indicated for prevention and treatment

- For women who cannot take bisphosphonates

- Risk of thrombosis, leg cramps and hot flashes

- Decreases LDL

- Breast cancer risk reduction

- Peptide hormone secreted by cells in the thyroid gland --> acts directly to reduce bone resorption by binding receptors of osteoclasts

- For treatment only

- For special patients:  Can't take bisphosphonates, have acute fractures, have chronic osteoporotic pain

- Either 200IU in one nostril every day, alternating nostrils, or 100 units sc (rare)

- Tolerated well but not as efficacious as other therapies

- Once considered first line for prevention and treatment in women

- WHI studies reveal that HRT does reduce fractures, but increases risk of breast cancer, stroke, MI, and VTE

- No longer recommend for treatment of osteoporosis

- DEXA testing every 1-2 years to monitor bone loss and efficacy of drug therapy

- Pharmacy services of counseling on Calcium and Vitamin D, proper administration of bisphosphonates, and prevention of steroid induced osteoporosis

- Pharmacists can play a key role in identifying secondary causes of osteoporosis

- DEXA testing is gold standard in determining BMD

- Calcium and Vitamin D supplementation are early counseling points

- Bisphosphonates are 1st line therapy

- Teriparatide (Forteo) is ONLY therapy that stimulates bone formation, good option for severe disease, but remember black box

- Raloxifene (Evista) may be alternative option for certain patient populations (intolerant to bisphosphates or high risk of cancer)