Osteoporosis

Definition of Osteoporosis:A condition of skeletal fragility characterized by:

• bone fragility predisposing to an increased risk of fracture.

• Low bone mass. • Low bone quality (trabecular micro-architecture).

Normal Bone Osteoporosis

PREVALENCE

• At age of 50 years: risk of hip fracture is:– 15% of white woman. – 5% of men.

• At age of 80 years: risk of hip fracture is:– 30% of women. – 15% of men.

Types of osteoporosis

(1) Involutional, or primary, osteoporosis, in which no underlying cause can be identified.

(2) Secondary osteoporosis, in which the underlying cause (eg, steroid use) is known.

(3) Rare forms of the disease, such as juvenile, pregnancy-related, and postpartum osteoporosis.

Pathogenesis1- Genetic factors: Polygenic.The single most significant influence on peak bone mass.2- Nutritional factors.3- Sex hormone status.4- Physical activity.

Risk factors • Endogenous factors:

– Female gender.– Advancing age.– Family history of fracture.

• Exogenous factors: – Hypogonadism (male or female).– Glucocorticoid treatment.– Low body mass index.– Previous fracture.– Smoking.– Immobilization.– Excess alcohol.– Vitamin D and calcium deficiencies in the elderly.

Risk factors• Endocrine disorders:

– Cushing's syndrome. – Hyperparathyroidism.– Thyrotoxicosis.– Insulin-dependent diabetes mellitus. – Acromegaly. – Adrenal insufficiency.

• Rheumatologic disorders: – Rheumatoid arthritis.– Ankylosing spondylitis.

• Hematologic disorders/malignancy :– Multiple myeloma.– Lymphoma and Leukemia. – Hemophilia. – Thalassemia.

• Nutritional and gastrointestinal disorders: – Malnutrition.– Parenteral nutrition.– Malabsorption syndromes.– Inflammatory bowel diseases. – Gastrectomy.– Severe liver or renal disease (especially biliary

cirrhosis). – Pernicious anemia.

Symptoms• Osteoporosis, the "silent disease," has bone loss

without symptoms.  • Onset only occurs with sudden strains, or fall causes

a fracture or a vertebra to collapse.  • Collapsed vertebrae may initially be felt or seen in

the form of severe back pain, loss of height, or spinal deformities such as kyphosis or stooped posture.

• Dowager’s hump (kyphosis + loss of height + cervical lordosis) present in severe cases.

• Peripheral fractures are more common in osteoporosis than hip and spine.

Diagnosis• Diagnosis is usually made following low

trauma fragility fracture as Colle’s , Vertebral, Hip, Proximal humerus, Rib, and Pelvic fractures.

• QCT: The best for trabecular bones.

High radiation dose & cost.• The gold standard is DEXA:

– Hip ± Spine (trabecular).

– Forearm in hyperpara. (cortical).

• Postmenopausal women who present with fractures.• Estrogen deficient women at clinical risk for osteoporosis. • Individuals with vertebral abnormalities. • Individuals receiving, or planning to receive, long-term glucocorticoid (steroid) therapy > 7 mg for > 3m.> 7 mg for > 3m.• Individuals with primary hyperparathyroidism. • Essential before ttt of osteoporosisEssential before ttt of osteoporosis to assess the response or efficacy of an approved osteoporosis drug therapy.

Who Should Be Tested?

• All women aged 65 and older.*• Younger postmenopausal women with multiple risk factors.

Bone Densitometry

DEXA scan: Hip

T-Score

WHO proposal for diagnosis of white postmenopausal osteoporosis

• >-1 SD -Normal• -1 to -2.5 SD -Low bone mass • <-2.5 SD -Osteoporosis• <-2.5 SD -Established + fragility fracture severe osteopo

T-score: SD of young adult peak mean value.-1SD = 10% bone loss

Other Bone Density Measurements

• Quantitative CT scanning :– Distinction between trabecular and cortical bone.– More expensive.– Higher radiation than other techniques.

• Quantitative ultrasound of the calcaneum: – Difficulties - Limited in routine use.

• Bone biopsy:– Bone biopsy may be useful in unusual forms of osteoporosis,

such as osteoporosis in young adults.– Biopsy provides information about the rate of bone turnover

and the presence of secondary forms of osteoporosis, such as myeloma and systemic mastocytosis.

Bone Markers• Alkaline phosphatase is derived from liver,

bone, kidney (and placenta). Bone-specific alkaline phosphatase is synthesized by osteoblasts; serum levels are raised in the growing child.

• Serum osteocalcin levels. • Pyridinoline or deoxypyridinoline are produced

by collagen degradation, and excreted in urine. Deoxypyridinoline is bone-specific, and both are more sensitive than urinary hydroxyproline.

How can we exclude an underlying cause ?

• CBC.• ESR.• Biochemistry.• RFT.• LFT: Alk phosphatase, Alb, AST, GT.• Ca, p, Alk ph.• TFT: TSH• Testosterone – LH (in men).

IN SPECIFIC SITUATION

• Estradiol – FSH if hormonal state is unclear as posthystrectomy.

• Serum and urine electrophoresis.

• Isotopic bone scan.

Treatment

Prevention

Calcium and Vitamin D Intake

• 400-800 Units per day.

Prevention

Lifestyle modification• Weight bearing exercise:

Jumping bone mass and walking fracture risk.• Prevent falls: Esp for hip fracture:

– Fall-proofing the houeshold.– Avoid drugs with dizziness & postural hypotension.– Hip protectors.

• Diet: balanced diet.• Vitamin B5 (Pantothenic acid) reduces bone loss.• Vitamin K is required for osteocalcin to function properly.• Avoid alcohol, smoking and caffeine.• Avoid  high amounts of calcium and Vitamin A.• Avoid high sodium retention negatively affects calcium /

magnesium.• Avoid long-term use of Aspirin or NSAIDs, reduce

magnesium and calcium.

Weight-Bearing Exercise

Consult your doctor first

Therapeutic Agents Used in Osteoporosis

• Inhibitors of bone resorption:– Calcium .– Estrogens +/- progest.– SERMs.– Bisphosphonates– Calcitonin.

• Stimulators of bone formation:– PTH.– Fluoride.

1- Ca 1200 mg/day for postmenopausal:

• Pure ca carbonate (taken with food).

• Pure ca citrate ( taken ± food).

2- Vitamin D: 400 for adults -800 for elderly adults IU/D ( multivitamin).

Pitfall : Calcitriol should not be given regularly

Risk for hypercalcemia.

Need plasma Ca monitor/3 m.

Bisphosphonates 1.Alendronate and alendronate plus vitamin D

(brand name Fosamax® and Fosamax® plus D). 2. Ibandronate (brand name Boniva®). 3.Risedronate and risedronate with calcium

(brand name Actonel® and Actonel® with Calcium).

4.Calcitonin (brand name Miacalcin®). Indications:Indications:

Steroid induced osteoporosisSteroid induced osteoporosis Men osteoporosis . Men osteoporosis . Prevention and treatment of osteoporosis. Prevention and treatment of osteoporosis.

Effect: Anti-fracture effect: inhibit osteoclast Effect: Anti-fracture effect: inhibit osteoclast function and decrease bone turnoverfunction and decrease bone turnover

Bisphosphonates:Dose:

Prevention: 5 mg/d or 35 mg/w.

ttt : 10 mg/d or 70 mg/w.

. Oral BPNs alendronate (Fosamax), risedronate (Actonel) have poor absorption rates and must be taken on an empty stomach with water.

Combination therapy with two antiresorptive agents is generally reserved for those who:

• Have experienced a fracture while on therapy with a single drug.• Start out with a very low BMD and a history of multiple fractures.• Have a very low BMD and lose more bone mass on therapy with a single drug.

Combination Therapy

Postmenopausal cases

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Estrogen / Hormone Therapy

1. Estrogens (brand names, such as Climara®, Premarin®) 2. Estrogens and Progestins (brand names, such as

Premphase®, Prempro®.3. Parathyroid Hormone – Teriparatide (PTH (1-34) (brand

name Fortéo®)

Selective estrogen receptor modulator (SERM) Raloxifene (Evista)

ACT on bone receptors and not breast or uterus receptors• Indications for prevention and treatment.• 60 mg/d. 40% BMD. 50% hip-spine fractures after 3 ys.• Risk:

– Menopausal symptoms : HOT FLUSH.– DVT & PE.– ?? CVD.

Calcitonin• Salmon calcitonin is a synthetic polypeptide that

duplicates the molecular structure of calcitonin found in the salmon fish.

• Salmon calcitonin is more potent than human calcitonin.• Nasal spray (Miacalcin) is the most convenient form.• approved by the FDA for treatment of postmenopausal

osteoporosis. Calcitonin inhibits osteoclast-induced bone resorption.

• Limited uses: Expense.• SE: allergy: salmon.• Strong analgesic.

PTH: Teriparatide Dose: 20 ug/d SC.

• Intermittent exposure to PTH can enhance bone mass.

65% Vertebral fracture.

• 53% Non-vertebral fracture.

• increased vertebral, femoral, and

total-body BMD.

Surgical Treatment

• Appropriate treatment of fragility fractures.

• Hip nailing.

• Kyphoplasty – Vertebroplasty.

How can you MONITOR ttt

• Max improvement occurs in 1st year.• Monitor BMD every 2 years. • Response to strong antiresorptive

agents effect is best seen in the spine. • EFFECTIVE TTT IF 5% RISE AT SPINE.• Use of biochemical markers:

– Formation: Alk Ph – osteocalcin.– Resorption: N- telopeptide.