Bone and Muscle Function

Osteoclasts

Bone resorption (breaks down bone)

Osteoblasts

Bone formation (secretes osteoid, promotes mineralization)

Osteocytes

Maintains bone matrix - maintains balance between resorption and remodelling

Bone lining cells

Regulate calcium exchange, surface maintenance

Effect of PTH (Parathyroid hormone) on bone

Increases Osteoclast activity and increases serum calcium

Effect of Vitamin D on bone

Increases calcium and phosphate absorption —→ promotes bone mineralization

Effect of Calcitonin on bone

Decreases osteoclast activity and decreases serum calcium

Bone Modeling

Formation of bone on sites where it has not been before

Bone Remodeling

The formation of bone on surfaces previously containing bone

So Bone Resorption is

Osteoclasts

Bone Formation are

osteoblasts

What is the bone remodeling cycle?

Resting, Osteoclasts resorption, reversal, and osteoblast formation

What are two clinically significant enzymes in Bone Formation?

• Alkaline Phosphatase (B-ALP)

• Osteocalcin

What does B- ALP do?

governs osteoclast activity, deposition of osteoid (uncalcified bone matrix), promoting mineralization

What is used to measure the amount os specific Bone ALP in the blood?

Ostase

What does Osteocalcin do?

Participates in regulation of mineralization or bone turnover

Most of the Osteocalcin produced is incorporated…

into bone matrix

What is the role of RANKL in bone metabolism?

It promotes osteoclast differentiation and activation, increasing bone resorption

What does osteoprotegerin (OPG) do?

Acts as a decoy receptor that binds RANKL and prevents osteoclast activation?

What effect does an increased RANKL/OPG ratiio have?

It leads to increased bone resorption

Which cells produce RANKL and OPG?

Osteoclasts

What is a commonly use biochemical marker of bone resorption derived from collagen breakdown?

C-termianl telopeptide (CTX)

What does an elevated level of N-terminal telopeptide (NTX) indicate?

Increased bone resorption

Which enzyme is a marker of osteoclast activity?

Tartrate resistant acid phosphatase (TRAP), especially TRAP 5b

What is deoxypyridinoine (DPD), and what does it reflect?

A collagen cross link released during bone degradation; it reflects bone resorption

Osteoporosis

The most common metabolic bone disease. It occurs when the rate of bone resorption is greater than the rate of bone formation or deposition

Potential causes of Osteoporosis

• decreased levels of estrogen and testosterone

• decreased activity level

• Inadequate Vit D and C, or Mg2+

Why is ALP increased in osteoporosis?

Due to increased osteoclast activity in response to high bone turnover

Why are N-telopeptides (NTX) elevated in osteoporosis?

They reflect increased collagen breakdown from elevated osteoclast activity (bone resorption)

Which is osteocalcin increased in osteoporosis?

It is a marker of bone formation and rises due to increased bone turnover, even though resorption exceeds formation

Why can Parathyroid hormone (PTH) be increased in osteoporosis?

It may increase in cases of Vitamin D deficiency, causing hyperparathyroidism and increased bone resorption

Why is 24H urine Ca decreased in osteoporosis?

Due to low calcium intake or absorption, leading the body to conserve Ca and reduce urinary excretion

Why Vit D 25 decreased in osteoporosis?

Due to inadequate intake, sunlight exposure, or absorption, resulting in reduced Ca absorption from the gut

Pagets Disease

Excessive resorption of spongy bone and accelerated formation of softened bone

What treatment is used for Paget’s Disease and Osteoporosis?

Bisphosphonates - Stimulates osteoclast apoptosis

What causes Rickets and Osteomalacia?

Caused by abnormal bone mineralization and Vit D deficiency

What is Rickets?

Occurs in growing bone —→ bony deformities from bending of long bones due to gravity

What is Osteomalacia?

Inadequate bone mineralization in the adult leading to soft bones. No deformities

Osteomyelitis is usually caused by…

Staphylococcal infection

Osteopetrosis

Condition due to functional deficiency of osteoclasts resulting in defective ossification producing excessive bone that is brittle and easily fractured

Osteogenesis Imperfecta

Also a brittle bone disease but is due to a collagen synthesis defect resulting in faulty ossification producing osteopenia and brittle bones

Of all diseases mentioned, which ones have decreased Ca and elevated PTH?

Osteomalacia/rickets

Of all diseases mentioned, which have elevated B-ALP?

Osteopetrosis and Osteomalacia/rickets

Osteosarcoma

Most common malignant bone tumor. Arises from knee with metastasis in lungs and represents 38% of bone tumors

Osteoclastoma/Giant cell tumor

Derived from fibrioblasts and osteoclasts

Osteoma

Affects the skull

Chondroblastoma

Arises from bone cartilage in the epiphyses of arms or leg bones

What is the difference between “arthritis” and specific conditions like osteoarthritis and rheumatoid arthritis?

Arthritis is a general term for joint inflammation, includes Osteoarthritis and RA

What is the main cause of Osteoarthritis?

Degeneration of articular cartilage due to wear and tear

What is the underlying mechanism of RA?

Autoimmune inflammation of the synovium leading to joint destruction

Muscle strain

Sudden, forced motion causing the muscle to become stretched beyond its normal capacity

Rhabdomyolysis (myoglobinuria)

Severe life threatening complication of severe muscle trauma with muscle cell loss

Muscular Dystrophy types

Diseases characterized by a genetic etiology and progressive degeneration of skeletal muscle. Duchenne, Becker’s, Myotonic, Facioscapulohumeral

A deficiency of … causes Duchenne disorder

Dystrophin

What is dystrophin?

Protein essential for stabilizing the sarcolemma and extracellular matrix

The deficiency of Dystrophin in Duchenne results in…

damage and tearing of muscle fibers during contraction causing muscle fiber generation. Begins age 5, by age 15-20 they are wheelchair or bed bound and soon dead

What is Becker’s disease?

A milder form of Duchenne with a longer life span (40s)

Describe Myotonic disease

Abnormal membrane channels causing atrophy and loss of strength. Myotonic muscles exhibit delayed relaxation after it contracts. Can affect cardiac and respiratory muscles

Facioscapulohumeral disease affects which muscles?

Muscles of face, neck, shoulders, and upper arms

Mitochondrial myopathies produce prominent muscular problems. Conditions that affect both muscle and nervous system are…

encephalomyopathies

What is the typical inheritance of Mitchondrial myopathies?

Inherited in maternal pattern. The variation in diseases occurs due to balance between normal and mutated mitochondria in cells

Which is examined to diagnosis mitchondrial myopathies?

History, Labs, ECG, Muscle biopsy, genetic testing

What happens to CK in muscle disease?

Increased - leakage from damaged muscle cell membranes

How are myoglobin levels affected in muscle disease?

Increased - released into blood from injured muscle fibers

What happens to LDH, AST, Aldolase, Carbonic Anhydrase in muscle diseases?

Increased - leaks from damaged muscle cells

Which troponin is increased in chronic muscle disease?

TnT