OSTEOPOROSIS

RISK FACTORS FOR OSTEOPOROSIS

MEDICAL DISORDERS AND MEDICATIONSASSOCIATED WITH OSTEOPOROSIS

MEDICATIONS KNOWN TO CAUSE OR ACCELERATE BONE LOSS Glucocorticoids

Excessive thyroid hormone

Diuretics: Furosemide

Cyclosporine, methotrexate, tacrolimus

Seizure medications: Phenytoin, phenobarbital

Psychotropic: Lithium,

Heparin

EVALUATION AND TREATMENT OF OSTEOPOROSIS Initial evaluation:

CBC Ca, p, Cr Alkaline phosphatase,

aminotransferases 25-hydroxyvitamin D TSH 24-hour urine for Ca and creatinine

ASSESSMENT OF BONE DENSITY Osteoporosis diagnosed when a radiograph

shows signs of demineralization or compression fractures of vertebral bodies.

Techniques for evaluating bone mass:

Dual-energy x-ray absorptiometry (DEXA)

Quantitative (CT) of spine.

Ultrasound

INDICATIONS FOR BMD All postmenopausal women < 65 yr who have one or

more additional risk factors for osteoporosis

All women > 65 yr regardless of additional risk factors

To document reduced bone density in patients with vertebral abnormalities or osteopenia on radiographs

To diagnose low bone mass in glucocorticoid-treated individuals

To document low bone density in patients with asymptomatic primary or secondary hyperparathyroidism

TREATMENTCalcium:

Goals of therapy for osteoporosis reduce bone resorption and enhance bone formation.

Bone loss occurs when Ca intake and absorption insufficient to balance daily Ca losses.

In absence of kidney stones or an underlying disorder of Ca metabolism,Ca intakes safe.

Calcium carbonate:

contains 40% elemental Ca

should be taken with meals because of poor absorption in achlorhydric patients in absence of food.

Calcium citrate:

contains 24% elemental Ca,

better bioavailability and is more absorbed.

absorbed well on an empty stomach in patients with achlorhydria.

Milk Yogurt Orange juice (with Ca) Cheese Ice cream (1/2 cup) Soy milk (1 cup) Beans (1/2 cup cooked) Dark,green vegetables

(1/2 cup cooked) Almonds Orange (1 medium)

300 mg 250 mg 300 mg 195 to 335 mg 100 mg 300 mg 60 to 80 mg 50 to 135 mg 70 mg 60 mg

SELECTIVE ESTROGEN RECEPTOR MODULATORS Tamoxifen:

Estrogen antagonist that binds to estrogen receptor

Estrogen-agonist effects on bone

Small increase in bone density of spine over 2 years,

No effect on radial bone density

45% reduction at hip and 29% at spine fracture.

Raloxifene:

FDA approved for prevention and treatment of

osteoporosis

Estrogen agonist on bone

Antagonist effects on breast and uterus.

Increased BMD in lumbar spine by 2.4%, in hip by 2.4%, in total body 2%

Over 2-year, significant reduction in vertebral fractures

CALCITONIN a potent inhibitor of osteoclastmediated bone

resorption.

Human and salmon calcitonin available

Salmon calcitonin commonly used because greater potency.

Parenteral calcitonin (100 IU SC or IM three times a week or daily)

Maintain bone density or produce a small increase in bone mass in spine

Nasal spray calcitonin absorbed through nasal mucosa

Approximately 40% as potent as parenterally administered (50 to 100 IU of injectable calcitonin comparable with 200 IU of nasal spray calcitonin).

Nasal calcitonin (200 IU/day) increases spinal bone density

No effect on proximal femur bone mass;

36% reduction in vertebral fractures over 5 years.

Adverse effects of parenteral calcitonin:

nauseaflushing

local irritation at injection site

Calcitonin intranasally well tolerated

Rhinitis and nasal dryness and crusting potential side effects.

Calcitonin may beneficial analgesic response in presence of osteoporotic fractures.

BISPHOSPHONATES

Alendronate (Fosamax) is FDA approved for prevention and treatment of osteoporosis.

Alendronate (10 mg/day) produces:

8.8% and 7.8% increase in bone density in spine and femoral trochanter

Alendronate (70 mg) most commonly used dose for treatment of osteoporosis.

Adverse effects of bisphosphonates:

GI symptoms:stomach painesophagitis

Myalgias and arthralgias,

Osteonecrosis of jaw

Subtrochanteric fractures

Risedronate:

Increased bone mass

Reduced risk of new vertebral fractures

Significant reduction in risk of hip fracture

Approved for prevention and treatment of osteoporosis(35 mg once a week)

Risedronate well tolerated even in patients with mild GI symptoms.

Ibandronate:

Approved for treatment and prevention of osteoporosis.

Vertebral fractures reduce about 50%.

150 mg/month

Intravenous ibandronate in a dose of 3 mg every 3 months

Zoledronic acid approved for treatment and prevention of osteoporosis.

5 mg once a year by intravenous infusion,

Risk of vertebral fractures reduce 68%, hip fractures 40%

Side effects:

arthralgias and myalagias;

Patients should have serum Ca and 25-OHD levels monitored and replaced to NL levels before treatment.

RANK LIGAND INHIBITOR Denosumab (Prolia):

Monoclonal antibody that against RANKL

Approved for treatment of osteoporosis.

60 mg subcutaneously every 6 months for 36 months

Vertebral fractures reduce 68%, hip fractures 40%,

Well tolerated,

Adverse events: skin infection

Before treatment Ca and 25-OHD should be checked and replaced if needed up to normal levels.

PARATHYROID HORMONE PTH significantly increase bone mass in

spine,

Fortéo approved for treatment of osteoporosis.

20 μg/day for 21 months.

Lumbar spine bone mass increased between 9% and 13% ,

Hip bone mass increased slightly.

Risk of new vertebral fractures reduce nearly 70%.

Fortéo is given daily injection.

Individual may experience headache, nausea, flushing with initiation of treatment, but these side effects become less severe after few weeks.

PTH:

Stimulates new bone formation

Increases bone mass

Reduces new vertebral and nonvertebral fractures

Subcutaneous injection daily for 18 to 24 months.

Other routes of administration:

intranasalskin patch.

VITAMIN D Physiologic doses of vitamin D

important to NL bone mineralization.

Individuals 50 years of age and older should take at least 600 to 1000 IU of vitamin D daily

Low vit D levels increase risk of bone loss and fracture.

Low 25-OHD levels during the winter and spring associated with decreases in bone density.

Daily treatment with 700 IU of cholecalciferol and 500 mg of Ca carbonate reduced rate of bone loss in:

femoral neck, spine,

total body Decreased incidence of nonvertebral fractures by

50%.

Patients require a vit D intake that in 25-OHD level of at least 30 ng/mL.

RECOMMENDATIONS FOR PREVENTION OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS Patients starting GC therapy at a dose equivalent to

prednisone ≥5 mg/day for 3 mo or longer should:

Modify risk factors for osteoporosis (stop smoking, decrease alcohol consumption)

Start regular weight-bearing physical exercise

Initiate intake of Ca (total 1500 mg/day) and vit D(400-800 I U/day)

BMD to predict risk of fracture and bone loss

Initiate bisphosphonate therapy (alendronate 5 mg/day or 35 mg/wk, or risedronate 5 mg/day or 35 mg/wk)

TREATMENT If T-score is < −1:

Risk factor modification including reducing risk of falls

Regular weight-bearing physical exercises

Ca and vit D supplementation

Bisphosphonate therapy (alendronate 10 mg/day or 70 mg/wk,or risedronate 5 mg/day or 35 mg/wk);

If bisphosphonates contraindicated or not tolerated, calcitonin as second-line agent, intravenous bisphosphonate (pamidronate or zolendronate), parathyroid hormone

Repeat BMD measurement annually or biannually