Metabolic Bone Disease Flashcards
Bone Remodeling Rank-L Signaling
RANK-L: Bone Resorption
OPG: Bone Resorption
FRAGILITY FRACTURES
caused BY Compromised Bone Strength (osteoporosis)
1.5 million/yr in US
Fragility Fractures Risk Factors
Previous Fractures (Increases Fracture Risk 5 Fold)
Age
Falls
Low Bone Mass
Resorption > Formation
Bone Mass is Lost
Non-modifiable Risk Factors for Low Bone Mass
Age Race Gender Family History Early Menopause
modifiable Risk Factors for Low Bone Mass
Low Calcium Intake Low Vitamin D Intake Estrogen Deficiency Sedentary Lifestyle Cigarette Smoking Excess Alcohol (> 2/day) Excess Caffeine (> 2/day) Medications
Pre-Fracture Diagnosis of Osteoporosis
Normal T-score > -1.0
Osteopenia T-score = -1.0 to -2.5
Osteoporosis T-score < -2.5
Dx made @ lowest site
T or F: Low Bone Mass is Not Always Osteoporosis
True
Eval of low bone mass
Calcium, Alkaline Phosphatase Creatinine (eGFR) 25 OH Vitamin D Total Testosterone (Men) Thyroid Stimulating Hormone (TSH) Tissue Transglutaminase IgA Antibody 24 Hour Urine Calcium, Sodium, Creatinine
Who to Treat in 2014?
- Anyone with a Fragility Fracture Vertebral Fracture Hip Fracture
- T-Score < -2.5
Osteoporosis Prevention
- Ca++
- Vit D
- Exercise
- Fall prevention
Osteoporosis Tx
- Anti-ResorptiveAgents: Bisphosphonates, Denosumab , Raloxifene, Calcitonin Estrogens
- Anabolic Agents: Teriparatide Romosozumab
What is Osteomalacia and Rickets?
- Impaired Bone Mineralization Resulting in Soft, Weak Bones
- Inadequate Calcium x Phosphate Product for Bone Mineralization
- Osteomalacia -Adults
- Rickets -Children
Phosphate Disorders
-Acquired Hypophosphatemia (dec Oral Intake renal loss)
-Congenital Hypophosphatemic Rickets:
“Vitamin D Resistant Rickets”
Renal Phosphate Wasting
Impaired 1,25 (OH)2 Vitamin D Formation
Features of rickets
Pain Deformities Muscle Weakness Short Stature
Features of osteomalacia
Pain Deformities Fractures
Lab findings in osteomalacia & Rickets
Low Serum Calcium low Serum Phosphate High Serum Alkaline Phosphatase High Serum PTH Low Urine Calcium
Radiologic findings in Rickets
- Deformities: Bowing of Long Bones &Flaring Ends of Long Bones
- Delayed Epiphyseal Calcification
Paget’s Disease of Bone
An Idiopathic Bone Condition Characterized by Excessive/Unregulated Bone Resorption and Formation Causes: -Genetic Predisposition -Chronic Paramyxovirus Infection -Linked w/ dog ownership
Mutation of Sequestosome 1/P62 Gene
- 40-80% of Paget’s Families
- SQSTMI: ubiquitin binding protein. Forms ubiquitinated chains that function as protein scaffolds for IL-1 and TNF induced NF-B activation, which regulates RANK signaling that controls osteoclast differentiation, activity and survival.
Development of Paget’s Disease Requires:
- Genetic Component:enhances osteoclast formation/reactivity
- Paramyxovirus Infection:induces changes in osteoclast precursors
Paget’s clinical features
- Skeletal: pain, fractures, deformity, fractures, etc
- Neurologic: deafness, CN & spinal compression
- CV: atherosclerosis, aortic stenosis, CHF
Describe the clinical progression of Paget’s
The disease progression starts w/:
- predominant bone resorption (Inc NTX/CTX)
- Equal resorption and formation (inc NTX & alk phos)
- Dec both, yet bone formation is higher (low NTX, high/low alk phos)
Bone remodeling markers
- Urine NTX / CTX (Resorption): seen early/mid paget’s
- Serum Alkaline Phosphatase (Formation) mid phase/late?
Paget’s radiology findings
-Osteolytic lesions: “blades of grass” in long bones
-Thickend, expanded cortex
-Expansion of bone size
Bone Scan: focal areas of intense uptake
Finding are usually very specific
Paget’s Histo findings
Increased Osteoclast Numbers
Increased Osteoclast Nuclei
Increased Osteoblasts in Periphery
Disorganized, Mosaic, Woven Bone
