Osteoperosis and Metabolic Bone Disorders Flashcards
Bone Remodeling
a. Body can recognize when bone is older
i. Osteoclasts will bind to older bone (can recognize a rough border of older bone)
b. Osteoclasts will secrete proteolytic enzymes and acid—> Release Ca and Phosphate
i. will also release stimulatory factors for osteoblasts
c. Osteoblasts will come in (attracted by stimulatory factors of osteoclast)
i. osteoblast will secrete Osteoid–> collagen for building new blood
d. Need adequate Ca and PO4 for with Oseoid to form a new bone
i. this process is calcifying and mineralizing the new bone
e. The osteoblasts will get trapped in the new bone, will become Osteocytes
i. Osteocytes are mechanoreceptors, will sense stress and remodel/strengthen new bone!
Bone Resportion
a. RANK-Ligand (RANK-L) is the main controller of bone resportion
i. will be secreted by osteoblasts
b. Osteoblasts will secrete RANK-L while they are in old bone, the RANK-L will bind to RANK on Osteoclasts
i. RANK activation will lead to increased stimulation of osteoclasts and bone breakdown
c. Decoy receptor is called OPG, will prevent RANK-L from binding to RANK
i. OPG will decrease the amount of osteoabsorption
d. RANK and OPG will battle for the amount of RANK-L that is secreted by Osteoblasts
i. More RANK activation means more bone resportion (breakdown and release of Ca and PO4)
ii. More OPG binding by RANK-L means LESS resportion
RANK-L: Rank Ligand
RANK: Receptor Activator of Nuclear Factor kb
OPG: Osteoprotegerin (decoy receptor for RANK-L)
Bone Formation
a. WNT pathway is the protein pathway that leads to osteoblasts forming new bones
i. Wnt, Frizzled / LRP-5, B-Catenin are major proteins of the WNT pathway for forming new bone
b. Sclerostin will inhibit the WNT pathway, and decrease new bone formation
Osteoperosis
a. Compromised Bone Strength
b. Predisposing to Increased Risk of FRAGILITY FRACTURES
i. think low trauma fractures (should not normally happen)
c. Fragility fracture is a type of pathologic fracture that occurs as result of normal activities, such as a fall from standing height or less. There are three fracture sites said to be typical of fragility fractures: vertebral fractures, fractures of the neck of the femur, and Colles fracture of the wrist. This definition arises because a normal human being ought to be able to fall from standing height without breaking any bones, and a fracture therefore suggests weakness of the skeleton
Osteoporosis Fragility Fractures (Low Trauma)
a. Most common areas of fragility fractures
Spine ~ 700,000/year in US
Hip ~ 300,000/year in US
Wrist ~ 250,000/year in US
b. Total Fragility Fractures: 1.5 million
c. Fragility Fractures = Osteoporosis
d. A pathologic fracture is a bone fracture caused by disease that led to weakness of the bone structure.
i. This process is most commonly due to osteoporosis
Fragility Fractures (Osteoporosis) Risk Factors
Biggest risk factors
- Age
- Falls
- Low Bone Mass
- Previous Fractures
Low Bone Mass and Fracture Risk
- Osteoporosis
i. Very low bone mass - Osteopenia
i. fairly low bone mass
Fracture Risk
Effect of Previous Vertebral Fracture
Found that patients are at greater risk for fractures if they had previous fractures
Vertebral Fracture
Fragility Fracture
Most common type of fragility fracture
Abnormal Bone Remodeling
Resorption > Formation
a. Osteoclast activity is greater than osteoblast activity
i. will exceed bone formation
b. Bone mass is overall lost
Risk Factors for Low Bone Mass
a. Non-Modifiable: Age Race Gender Family History Early Menopause
b. Modifiable: Low Calcium Intake Low Vitamin D Intake Estrogen Deficiency Sedentary Lifestyle Cigarette Smoking Excess Alcohol (> 2/day) Excess Caffeine (> 2/day) Medications
Differential Diagnosis of Low Bone Mass
Low bone mass is not always osteoperosis
Osteoporosis
i. the most common cause by far
Osteomalacia Osteogenesis Imperfecta Hyperparathyroidism Hyperthyroidism Hyperprolactinemia Hypogonadism Cushing’s Syndrome Eating/Exercise Disorders
Celiac Disease Inflammatory Bowel Dz Primary Biliary Cirrhosis Multiple Myeloma Rheumatoid Arthritis Chronic Renal Failure Renal Tubular Acidosis Idiopathic Hypercalciuria Systemic Mastocytosis
High Risk Medications*
i. Well Established: Glucocorticoids, Excess Thyroid Hormone, Anticonvulsants
ii. Probable/Possible: Thiazolidinediones, SGLT2-I’s, SSRI’s, PPI’s
Osteoporosis Prevention and Treatment
a. Calcium: 1000-1500 mg/day
b. Dairy Products (CaPO4): ~ 300 mg/serving
c. Supplements if Dairy Intake Insufficient
d. Vitamin D: 1000 units/day
e. Exercise: Aerobic and Resistance
f. Falls: Assessment and Prevention
Osteoporosis Treatment Strategy
Alter Bone Remodeling
Medications that
1. Decrease Bone Resorption
OR
2. Increase Bone Formation
Osteomalacia and Rickets
a. Impaired Bone Mineralization Resulting in Soft, Weak Bones
b. Not mineralizing properly (unlike osteoporosis, where there is net loss)
Osteomalacia - Adults
Rickets - Children
Osteomalacia and Rickets
Pathophysiology
a. Inadequate Calcium x Phosphate
i. Product for Bone Mineralization
b. Have more Unmineralized Osteoid
i. soft bone that is weak
[Ca x PO4 < 24]
Vitamin D Disorders
Can lead to osteomalacia
a. Acquired Vitamin D Deficiency
i. Poor Oral Intake / Malabsorption
ii. Inadequate Sunlight
b. Acquired 1,25 (OH)2 Vitamin D Deficiency
i. Renal Disease
ii. Hypoparathyroidism
c. Congenital 1 Alpha Hydroxylase Deficiency
i. “Vitamin D Dependent Rickets Type 1”
d. Congenital Vitamin D Receptor Deficiency
i. “Vitamin D Dependent Rickets Type 2”
Phosphate Disorders
Can lead to osteomalacia
a. Acquired Hypophosphatemia
i. Poor Oral Intake
ii. Renal Phosphate Wasting
b. Congenital Hypophosphatemic Rickets
“Vitamin D Resistant Rickets”
i. Renal Phosphate Wasting
ii. Impaired 1,25 (OH)2 Vitamin D Formation
Clinical Features of Osteomalacia and Rickets
a. Osteomalacia:
Pain
Deformities
Fractures
b. Rickets: Pain Deformities Muscle Weakness Short Stature
Rickets
a. Rickets is defective mineralization or calcification of bones before epiphyseal closure in immature mammals due to deficiency or impaired metabolism of vitamin D, phosphorus or calcium potentially leading to fractures and deformity.
b. An X-ray or radiograph of an advanced sufferer from rickets tends to present in a classic way: bow legs (outward curve of long bone of the legs) and a deformed chest.
i. Changes in the skull also occur causing a distinctive “square headed” appearance (Caput Quadratum).
ii. These deformities persist into adult life if not treated. Long-term consequences include permanent bends or disfiguration of the long bones, and a curved back.
Osteomalacia is a similar condition occurring in adults, generally due to a deficiency of vitamin D but occurs after epiphyseal closur