Osteopenia and osteoporosis

Osteopenia refers to decreased bone mass.
Osteoporosis refers to osteopenia (reduced bone strength/mass) that is severe enough to increase the risk of fracture.
According to WHO, osteoporosis is defined as bone mineral density that falls 2.5 standard deviation below mean for young healthy adult of same sex and race.


Osteoporosis associated fractures :
These are adulthood fractures of any bones (chiefly hip and vertebral fractures) in the setting of trauma less than or equal to fall from standing height with exception of fingers, toes, face and skull.

Drugs associated with osteoporosis
Alcohol
Glucocorticoids
Anticoagulants
Anticonvulsants
Chemotherapy
Excess thyroxine

Endocrine disorders
Cushing syndrome
Hyperparathyroidism
Thyrotoxicosis
Diabetes mellitus (both type I and II)
Acromegaly

CATEGORIZATION OF OSTEOPOROSIS

A.Primary

Idiopathic
Postmenopausal
Senile/age related

B. Secondary (Diseases)

Hypogonadal state, endocrine disorders, nutritional and gastrointestinal disorders, rheumatologic disorders, hematological disorders/malignancy, inherited disorders and others.

Usually asymptomatic until fracture occurs
Vertebral and hip fracture common by simple fall
Loss of height due to multiple vertebral fracture and other deformities like lordoisis, kyphoscoliosis.
Fracture of femur neck, pelvis or spine causes deep vein thrombosis and pulmonary embolism, pneumonia.

INVESTIGATIONS FOR OSTEOPOROSIS

DXA (Dual energy X-ray absorptiometry)
Quantitative CT
Ultrasound
Urea, creatinine and electrolytes
Liver function test and albumin
Renal function test
Full blood count, ESR
Serum calcium and phosphate
Serum vitamin D and alkaline phosphate
Serum PTH
Thyroid function test
Testosterone, estrogen and gonadotropins
Serum cortisol
Bone biopsy
Plain radiography not diagnostic

Following non pharmacological approaches are taken:

Exercise
Appropriate calcium and vitamin D intake (Calcium 1000mg/day and vitamin D 800 IU/daily)
Cessation of smoking
Limit/ Quit alcohol intake
Get up and go exercise
Hip protectors to reduce the risk of fracture.

Pharmacological agents

Bisphosphonates ( decrease osteoclast activity)
Postmenopausal hormone replacement therapy
Denusumab (anti- RANKL antibody)
Anti- sclerostin antibodies
Cathepsin k antibodies

1. OSTEOPENIA AND OSTEOPOROSIS Medical MADE EASY

2. Osteoporosis associated fractures : These are adulthood fractures of any bones ( chiefly hip and vertebral fractures ) in the setting of trauma less than or equal to fall from standing height with exception of fingers, toes, face and skull. OSTEOPENIA AND OSTEOPOROSIS Osteopenia refers to decreased bone mass. Osteoporosis refers to osteopenia (reduced bone strength/mass) that is severe enough to increase the risk of fracture. According to WHO , osteoporosis is defined as bone mineral density that falls 2.5 standard deviation below mean for young healthy adult of same sex and race. Modifiable risk factors od osteoporosis Cigarette smoking Estrogen deficiency( most common-postmenopausal) Low calcium and vitamin D diet Alcoholism Inadequate physical exercise Non-modifiable risk factors of osteoporosis History of fracture in 1 st degree relatives Female gender Advanced age White race Dementia Personal history of fracture as an adult

3. EPIDEMIOLOGY Most common bone disease. Approximately 8.9 million fractures occur annually worldwide and most of them are osteoporosis associated fractures . 1/3 of women and 1/5 of men after the age of 50 suffer from such fracture. Most common are postmenopausal and senile osteoporosis . Occurs mostly in elderly female but can occur in both sexes with underlying disease and risk factors . In women , loss of ovarian function after menopause( > 50 years of age) leads to rapid bone loss with risk of osteoporosis by the age of 70-80 . Endocrine disorders Cushing syndrome Hyperparathyroidism Thyrotoxicosis Diabetes mellitus (both type I and II) Acromegaly Selected inherited disorders Osteogenesis imperfecta Marfans’s syndrome Hemochromatosis Glycogen storage disease Homocystinuria Ehlers- Danlos syndrome Epidermolysis bullosa CATEGORIZATION OF OSTEOPOROSIS Primary Idiopathic Postmenopausal Senile/age related B. Secondary (Diseases) Hypogonadal state, endocrine disorders, nutritional and gastrointestinal disorders, rheumatologic disorders, hematological disorders/malignancy, inherited disorders and others . Drugs associated with osteoporosis Alcohol Glucocorticoids Anticoagulants Anticonvulsants Chemotherapy Excess thyroxine Hypogonadal states Turner’s syndrome Klinefelter’s syndrome Hypothalamic amenorrhea Anorexia nervosa Hyperprolactinaemia Hematological disorders/ malignancy Multiple myeloma Lymphoma and leukemia Mastocytosis Nutritional and gastrointestinal disorders Malnutrition Malabsorption syndrome Gastrectomy Parenteral nutrition Pernicious anemia Biliary cirrhosis Others Immobilization COPD Pregnancy and lactation Sarcoidosis and amyloidosis Multiple sclerosis Rheumatologic disorders Rheumatoid arthritis Ankolysing spondylitis

4. PATHOPHYSIOLOGY Peak bone mass or bone mineral density (BMD) is determined by hereditary factors, physical exercise, muscle strength, diet and hormonal status . Following are the well known theories regarding the pathogenesis of osteoporosis. Age related changes (senile): Osteoblasts of older individuals are less active than that of younger population. So there is diminished bone matrix formation in elderly people. This is known as senile osteoporosis. b. Reduced physical exercise : Experimentally, it is seen that reduced physical exercise increases the rate of bone loss . There is bone loss in : Elderly people with diminished physical work Immobilized or paralyzed part of body Astronauts in zero gravity for prolonged time. There is high bone mineral density in athletes. It is seen that load magnitude of physical exercise increases bone density than the number of load cycles. It implies that weight training are more effective for increasing bone mass than repetition of exercise. c . Genetic factor Defect in LRP5 gene Over expression of RANKL and RANK receptor and less expression of osteoprotegerin stimulates osteoclast formation and recruitment leading to bone resorption. d. Calcium and vitamin D nutritional state Lack of calcium and vitamin D during growing age of life increases the risk of osteoporosis in later life. Lack of calcium , increases PTH and reduced vitamin D level contribute to osteoporosis. e. Hormonal influence Postmenopausal osteoporosis is due to estrogen deficiency as a result of cessation of ovarian function. Decreased level of estrogen increases the release of inflammatory cytokines like IL-1, IL-6, TNF that in turn, increases the production of RANKL, RANK receptor and reduces the expression of osteoprotegerin, increasing osteoclast formation and recruitment.

5. CLINICAL FEATURES OF OSTEOPOROSIS Usually asymptomatic until fracture occurs Vertebral and hip fracture common by simple fall Loss of height due to multiple vertebral fracture and other deformities like lordoisis , kyphoscoliosis . Fracture of femur neck, pelvis or spine causes dee p vein thrombosis and pulmonary embolism, pneumonia .

6. INVESTIGATIONS FOR OSTEOPOROSIS DXA (Dual energy X-ray absorptiometry) Quantitative CT Ultrasound Urea, creatinine and electrolytes Liver function test and albumin Renal function test Full blood count, ESR Serum calcium and phosphate Serum vitamin D and alkaline phosphate Serum PTH Thyroid function test Testosterone, estrogen and gonadotropins Serum cortisol Bone biopsy Plain radiography not diagnostic ALGORITHM FOR THE INVESTIGATION OF PATIENTS WITH OSTEOPOROSIS Osteopenia Screen for secondary cause Age >50 Low trauma fracture Age>50 Fracture risk> 10% DXA spine and hip Age<50 Very strong risk factors Normal Reassess at later date Correct modifiable risk factors Correct modifiable factors + give drugs Osteoporosis

7. TREATMENT AND PREVENTION OF OSTEOPOROSIS Aim is t o reduce the risk of fractures. Following non pharmacological approaches are taken: Exercise Appropriate calcium and vitamin D intake (Calcium 1000mg/day and vitamin D 800 IU/daily) Cessation of smoking Limit/ Quit alcohol intake Get up and go exercise Hip protectors to reduce the risk of fracture. Surgical approach Orthopedic surgery with internal fixation to stabilize osteoporotic fractures. Hemiarthroplasty or total hip replacement Vertebroplasty Pharmacological agents Bisphosphonates ( decrease osteoclast activity) Postmenopausal hormone replacement therapy Denusumab (anti- RANKL antibody) Anti- sclerostin antibodies Cathepsin k antibodies