Calcium Metabolism Disorders

Question 1

Role of Calcium

Answer 1

Critical for mineralization of the skeleton
- Creates bone strength and structure

Bone is the metabolic reservoir to maintain the intra and extracellular calcium
- The remainder of calcium is in blood, extracellular fluids, muscles and other tissues
- Calcium is responsible for mediating muscle contraction, vascular contraction and vasodilatation, nerve impulse transmission, and intra and extracellular signaling
- Hormones are responsible to keep the serum Ca levels WNL to maintain homeostasis

Question 2

Normal Bone Metabolism

Answer 2

Bone is constantly remodeling
- Balance of formation and resorption

Osteoblasts: bone formation
- Produce and secrete the unmineralized matrix of Type I collagen and proteins that then becomes mineralized

Osteoclasts: Bone resorption
- Break down mineralized bone

Question 3

Phases of Bone Remodeling

Answer 3

Inactive
Activation
Resorption
(Reversal)
Formation
Mineralization

Question 4

Inactive

Answer 4

Prior to initiating remodeling
Event triggers activation (loading, micro trauma, diet)

Question 5

Activation

Answer 5

Osteoclast precursors attach to bone surface

Question 6

Resorption

Answer 6

Osteoclasts degrade bone and free growth factors

Question 7

Reversal

Answer 7

Osteoclasts create pits
Macrophages come in to clean up and prevent erosion

Question 8

Formation

Answer 8

Collagen mineralized matrix (from osteoblasts) fills the cavity

Question 9

Mineralization

Answer 9

Osteoblasts secrete matrix vesicles to increase calcium and phosphorus
Takes 3-6 months

Question 10

Cortical vs Trabecular Bone Remodeling

Answer 10

40% of trabecular and 10% of cortical bone is remodeled annually

Question 11

Bone Metabolism

Answer 11

Regulated by PTH, calcitonin, calcitriol (hormonal Vit D)

With low serum Ca, osteoclasts break down bone due to↑PTH
- But then the thyroid secretes calcitonin to activate osteoblasts
- PTH↑s Vit D synthesis which then↓s PTH

With high serum Ca, calcitonin blocks osteoclasts to↓ serum Ca
- Vit D helps by blocking release of Ca from kidneys

Question 12

Influencers of Bone Metabolism

Answer 12

Skin: Impacts Vit D synthesis

Liver/Kidneys: D3 is converted into pre- hormonal form of Vit D in the liver and kidneys

Small intestine: absorbs calcium

Thyroid gland: Hormones critical for skeletal growth & bone mass - Meds to treat hypothyroidism may↑ rate of bone loss

Parathyroid gland:
Hypo: ↓s remodeling and↑bone mass too much
Hyper:↑s osteoclastic activity

Pituitary gland: secretes growth hormone

Question 13

Osteoporosis

Answer 13

Systemic skeletal disease marked by decreased bone mineral mass and compromises in bone architecture

Clinical definition is bone density 2.5 standard deviations below the healthy adult mean as measured by DXA scan

Question 14

Primary Osteoporosis Causes

Answer 14

Aging: After 30 years of age, osteoblastic activity decreases (net bone loss of 0.5% of total mass/year)

Menopause: Declining estrogen levels result in increased osteoclastic activity (net bone loss of 1–3% per year)

Men lose ~ 30% trabecular and ~20% cortical bone in their lifetime

Women lose ~50% trabecular and 1/3 cortical bone in their lifetime

Question 15

Secondary Osteoporosis

Answer 15

Occurs at any age and has identifiable causes

Osteogenesis imperfecta
Hypogonadism: ↓s testosterone
Hyperthyroidism/Hypoparathyroidism
Hyperadrenalism: ↑ed cortisol
Diet-related: eating disorders
Medication-related
Hyperglycemia: alters bone metabolism
Autoimmune diseases
Neurologic diseases/diagnoses

Question 16

Osteoporosis Risk Factors

Answer 16

Non-Modifiable:
Family history
Asian or Caucasian race
Female
Post-menopausal

Modifiable:
Nutrition
Physical Activity
Smoking
Low Body Mass
Caffeine/Alcohol Consumption

Question 17

Race and Bone

Answer 17

Black children have greater bone mass, density, and more favorable bone architecture than white children

Osteoporosis: Less in non-Hispanic blacks compared to non-Hispanic whites, Hispanics and Asians

Question 18

Muscle and Sarcopenia

Answer 18

Sarcopenia is a universal aging phenomenon

Operationally defined as skeletal muscle mass greater than two standard deviations below the healthy adult

Question 19

Frailty

Answer 19

Frailty significantly associated with:
- Osteoporosis
- Hip fracture
- Recent falls

Frailty and pre-frailty are significant predictors of fractures among community- dwelling older people

Question 20

Clinical Diagnosis

Answer 20

DXA:
T score: compared to healthy young person
-1-2.5 SD = low bone mass
>-2.5 SD = osteoporosis
Z score: sex and age matched

Fractures—particularly of hip, distal radius, vertebrae •
Kyphosis of thoracic spine
Low BMI or low lean tissue mass
Advanced age
Presence of secondary causes of low bone mass

Question 21

Screening/Diagnosis

Answer 21

Osteoporosis Self-Assessment Tool:
- High risk: score less than –3
- Moderate risk: score 1 to –3
- Low risk: score greater than 1

SCORE Screen:
Simple Calculated Osteoporosis Risk Estimation: Score of ≥ 6 requires a DXA

FRAX: Risk Assessment

Question 22

Osteoporosis Treatment

Answer 22

Exercise!

Drugs focus on different phases of remodeling: Decreased resorption and increased formation

Question 23

Fractures

Answer 23

Significant reduction in fracture callus size, BMD, and mechanical strength at 3 weeks post-fracture indicating early failure of the repair process.

Quality of callus suggests a delayed healing process

Temporal changes in cellular differentiation include prolonged phase of endochondral calcification, higher phase of bone turnover.

Intervention with a first dose of bisphosphonates prior to leaving the hospital is important

Question 24

Osteomalacia

Answer 24

Decreased absorption of calcium and phosphorus in intestine due to disturbances in vitamin D metabolism
Increased PTH secretion
Decrease in bone formation

S&S:
Soft bones - Decreased mineralization
Fractures
Non-specific bone pain: dull, achy
Bone deformities
Possible muscle weakness over time

Question 25

Rickets

Answer 25

Increase in uncalcified matrix in bones and at the epiphyseal plates

Pediatric osteomalacia

S&S:
Convulsions
Tetany
Irritability
Delayed physical development
Weakness, failure to thrive
Deformities: genu valgum or genu varum
Small stature

Question 26

Paget’s Disease

Answer 26

Osteitis deformans - Disrupts replacement of old bone tissue with new bone tissue, has 3 distinct phases

Osteolytic phase - Increased osteoclastic activity

Mixed phase - Osteoclastic activity is counterbalanced by new bone formation

Osteclerotic phase - Increased bone deposition

S&S:
Bone pain, fractures
Cranial nerve entrapment
Spinal stenosis
Highly vascularized bone that can cause issues with orthopedic surgery
Progressive deformities of tibia, femur, pelvis, vertebral bodies, and skull

Question 27

Osteogenesis Imperfecta

Answer 27

Congenital osteoporosis (1/20,000 live births)

Failure of ossification due to defective collagen synthesis

S&S:
Cortical and trabecular bone are thin
Prone to pathological fractures
Prone to gross deformities due to multiple microfractures
Spinal curvature
Loose joints due to muscle weakness
Hearing loss