CORTEXT 1 - Basic Sciences BIOCHEM Flashcards
Define Osteoporosis clinically, and the WHO definition
Quantitive defect of bone - reduced bone density and increased porosity, leading to increased fragility and increased fracture risk
WHO - bone mineral density less than 2.5 standard deviations below the mean peak value of young adults of the same race and sex.
What is Osteopenia?
an intermediate stage where bone mineral density is between 1 and 2.5 SD below mean peak.
What mechanism causes the physiological loss of bone mineral density?
Gradual slow down in osteoblastic activity (after aged 30)
What are the two types of primary osteoporosis?
Type 1 Post Menopausal
Type 2 Osteoporosis of old age with a greater than expected decline
What are the risk factors for both types of primary osteoporosis?
Smoking
Alcohol
Poor diet
Lack of Exercise
Type 1 specific - early menopause, familial and environmental factors, white caucasians
Type 2 specific - chronic disease, reduced sunlight exposure.
What type of fractures commonly occur in the two different types of osteoporosis?
Type 1 - Colles, Vertebral insufficiency
Type 2 - Femoral neck, Vertebral
What conditions may secondary osteoporosis occur following?
Corticosteroid use
Alcohol Abuse
Malnutrition
Chronic disease including CKD, malignancy, RA
Endocrine disorders including Cushing’s, Hyperthyroidism, Hyperparathyroidism
How is Osteoporosis Diagnosed?
DEXA scanning to measure bone mineral density, compare with standard peak values
NB - Serum calcium and phosphate are normal
What is the treatments for Osteoporosis?
Prevention by building bone density when younger
Calcium and Vit D Supplementation
Biphosphonates (alendronate, risendronate, etidronate) for reducing osteoclastic resorption
Desunomab (monoclonal AB) to reduce osteoclast activity
Strontium (increase osteoblast replication)
Can give Zoledronic Acid once yearly IV biphosphonate, but this is expensive
HRT or Raloxifene can be used is SEs with other medications
NB - treatment aims to slow progression, not build bone mineral density
What is Osteomalacia?
Qualitative defect of bone with abnormal softening due to deficiency of mineralisation of osteoid, secondary to inadequate calcium and phosphorus
Rickets = osteomalacia in children, subsequent effects of growing skeleton
Causes of Osteomalacia
Insufficient calcium absorption from the intestine due to lack of dietary calcium, or a deficiency/resistance of vitamin D
Phosphate insufficiency due to increase renal losses
Malnutrition Malabsorption Lack of sunlight Hypophosphataemia Long term anticonvulsant use CKD Inherited renal disorders
How does Osteomalacia present?
Bone pain (pevis, spine, femora)
Deformities (e.g. rickets)
Easily sustain pathological fractures
Symptoms of hypocalcaemia – paraesthesiae, muscle cramps, irritability, fatigue, seizures, brittle nails
What can be seen upon clinical investigation for Osteomalacia?
Radiographs may show peusdofractures (Looser’s zones) of pubic rami, proximal femora, ulna and ribs
Serum biochemistry is abnormal - low calcium, low serum phosphate, high serum alkaline phosphatase
Treatment of Osteomalacia?
Vitamin D therapy with calcium and phosphate supplementation
What is Hyperparathyroidism?
Overactivity or the parathyroid glands, with high level of PTH
What causes the three types of hyperparathyroidism?
Primary - benign adenoma, hyperplasia, malignant neoplasia
Secondary - physiological overproduction due to hypocalcaemia due to vit D deficiency or CKD
Tertiary - chronic secondary + adenoma
What are the symptoms of Hyperparathyroidism?
fatigue depression bone pain myalgia nausea thirst polyuria renal stones osteoporosis
NB - symptoms are of hypercalcaemia due to overproduction of PTH
What is Renal Dystrophy?
Bone changes due to CKD
Reduced phosphate excretion and inactive activation of vit D -> secondary hyperparathyroidism -> osteomalacia, sclerosis of bone, calcification of soft tissues
What is Paget’s Disease?
Thickened, brittle misshapen bones due to increased osteoclast and osteoblast activity
What are causes of Paget’s?
Genetic defects Viral infection (paramyxoviruses)
What are the most commonly affected areas in Paget’s?
Pelvis Femur Skull Tibia Ear Ossicles (conductive deafness)
How does Paget’s Disease present?
Incidental finding @ XR Arthritis Pathological fracture Deformity Pain High output cardiac failure
Ix findings for Paget’s Disease
Serum alkaline phosphatase raised
Calcium and phosphorus normal
Radiology - enlarged bone, thickened cortices, coarse trabeculae, mixed areas of lysis and sclerosis
Bone scan - marked increase uptake in affected bone
Treatment of Paget’s Disease?
Biphosphonates (inhibit osteoclasts)
Calcitonin if lytic disease
Joint replacement may be required
Fractures stabilised with long intramedullary nails/plates
