Physiology of Bone😊

• No man’s land in flexor tendon → Zone 2

• Infertility workup → WHO grade 2 is most common

• BE FAN VEIN

• Patellar clunk syndrome

HLA associations

• Mnemonic: when Looser (Loosers zone) is in malasia () → stress () relieved → parts protrude (protrusio acetabuli) → like a cod fish mouth (cod fish) → Pelvis become radiated (Triradiate pelvis)

• Pseudofractures with surrounding sclerosis.:
• Also known as Milkman's Line or Looser Zone.
• Most common sites:
• Neck of femur >
• clavicle
• ribs
• pubic rami

• Stress fractures
• that have healed with mineral-deficient material.

• Triradiate pelvis

• Codfish or fish mouth vertebrae
• Biconcave vertebral bodies (after >30% bone loss).
• also in osteoporosis

• Protrusio Acetabuli: 
• Head of femur protrudes into the acetabulum.

Rugger Jersey Spine: 

• Alternating sclerotic and lucent bands,

• [Resemble stripes on a rugby jersey]

• Seen in
• Osteopetrosis
• Renal osteodystrophy - Secondary hyperparathyroidism

• Mnemonic:
• Mnemonic: Rugger jersey → look like rods → ROD → Renal osteodystrophy
• Rugby Jersey ittond marble (Osteopetrosis/marble bone ds) panikk poi → Got CKD ()

• Bony ankylosis → TB Spine

• Fibrous ankylosis → TB knee/hip

Triangles

• Babcock Triangle → TB hip

• Fairbank triangle → Congenital coxa vara (Trendelenberg gait/Waddling gait)

• Ward triangle → Osteoporosis

Osteoporosis

• Dexa Scan → Bone Mineral Density Scan

• Used to measure bone mineral density.

• Important for diagnosing osteoporosis.
• Biochemical tests are normal in osteoporosis.

T-score: 

• Compares bone mineral density
• to a young male/female (30 y.o.)
• with highest bone density.

• Quantitative CT (QCT)
• Not usually done, but can be done
• can also diagnose osteoporosis.

X-ray findings:

• Vertebral fracture.

• Neck of femur fracture.

• Colles' fracture.

• Codfish Vertebrae: 
• Biconcave vertebral bodies (after >30% bone loss).
• Also seen in Osteomalacia

• Fishmouth vertebra in osteoporosis:
• Decreased vertebral height.
• Vertebral collapse with concave end plate.

Drugs in Osteoporosis

• PTH stimulate Osteoclast → Cause osteoporosis

• Calcitonin inhibit Osteoclast → Prevent osteoporosis

• Drugs ending with “tide” → always IV

• Mnemonic:
• den OS mab , Rem OS mab
• → Antibody against osteoporosis

• Drugs used in osteoporosis
1. Nutritional factors:
• Calcium (1200 mg/day, includes dietary).
• Vitamin D (800 IU per day).
2. Drugs inhibiting osteoclast:
• Calcitonin
• Estrogens
• SERMs
• Denosumab
• Cinacalcet
• CasR agonist
• Used in HyperPTH
3. Drugs stimulating osteoblast:
• PTH1-34 → Teriparatide, Abaloparatide → Max: 2yrs (↑↑ R/o Osteosarcoma)
4. Drugs with Dual action:
• Strontium
• Romosozumab → Sclerostin ⛔ → Made in India
• Also Sodium fluoride

Drugs Inhibiting Osteoclast

1. Calcitonin: 
• Given Intranasally.
• S/E: Liver toxicity, Ca Breast

2. Bisphosphonates:
• Alendronate (oral)
• Risedronate (oral)
• Alan () rise () and eat
• Pamidronate (IV)
• Zoledronate (once yearly IV → Longest acting → S/E: Renal failure)
• Inhibit osteoclasts.
• DOC for
• Osteoporosis (any reason).
• Osteogenesis Imperfecta
• Pagets
• Indicated for a maximum of 10 years.
• 5 years → do bone scan → another 5 years
• IV agents can be also used for Hypercalcemia of malignancy
• S/E
• Osteonecrosis of mandible
• Phossy jaw
• Actinomyces → Discharging sinuses
• Radiotherapy
• Bisphosphonates
• Highly toxic to esophagus.
• Prevention of Esophagitis:
• Take empty stomach.
• Take with full glass of water.
• Remain upright for 30 min.
• Prolonged use (5-7 years)
• ↓↓ osteoclastic activity (below osteoblastic activity)
• → Atypical Fractures around the hip
• NEXT step: Do Xray, NOT DEXA
• Drug Holiday: 
• to avoid Atypical fractures
• Temporarily stop using bisphosphonates (1-2 years)
• switch to other drugs (e.g., Teriparatide)

3. Estrogen and SERM
• Decreased estrogen causes post-menopausal osteoporosis.
• Actions of Estrogen:
• Bone → Prevent resorption.
• Blood → Increased HDL/LDL Ratio.
• Breast → Increased Risk of Carcinoma.
• Endometrium → Increased Risk of Carcinoma.
• Liver → Increased Clotting Factors → Thromboembolism.
• Not preferred for treatment of post-menopausal osteoporosis.
• Raloxifene:
• Selective estrogen receptor modulator (SERM).
• Agonist action on ER in bone, blood, liver;
• antagonistic action on breast, endometrium.
• Used in post-menopausal osteoporosis.
• Reduces only vertebral # risk
• (Bisphosphonates reduce both vertebral and non vertebral)
• Additional Benefits:
• Increased HDL.
• Decreased Breast and Endometrial carcinoma risk.
• Major S/E:
• Thromboembolism.
• Tamoxifene → ↑ endometrial cancer risk

4. Denosumab:



• Monoclonal antibody → ⛔ RANK ligand.
• ⛔ osteoclastic activity and bone resorption.
• Mnemonic: Rank (RANK L) nu anserich Dinosaur (Denosumab) nte adth vidum → Clash cheyyan (Clast)

Drugs Stimulating Osteoblasts

Teriparatide:

• Fraction of parathyroid hormone (PTH 1-34)
• Intermittent low-dose PTH (Teriparatide) → stimulates osteoblast activity more than osteoclasts → bone formation.

• Used for osteoporosis treatment.

• Only anabolic agent for new bone formation

• Black box warning
• Use < 2 yrs
• ↑ risk of osteosarcoma
• Avoid in patients with increased risk of osteosarcoma
• Paget's disease
• Unexplained elevated ALP
• Open Epiphysis
• Prior radiation to skeleton

• Candidates
• Women with osteoporotic #
• Men with Primary or hypogonadal Osteoporosis
• Intolerant to other therapy

• Not effective orally
• OD subcutaneously

• Recommended for maximum 2 years.

• Treatment should be preceded or followed by bisphosphonates.

NOTE: PTH Action on Bone Cells

• PTH does NOT act directly on osteoclasts.

• Osteoclasts lack PTH receptors.

• PTH acts on osteoblasts → they release RANKL & M-CSF.

• These stimulate osteoclast differentiation and activation → ↑ bone resorption.

Drugs with Dual Action

• Stimulate osteoblast and inhibit osteoclast.

• Strontium ranelate and romosozumab.

• Romosozumab is a monoclonal antibody against sclerostin.

• Mnemonic: Romans (Romosumab) had Strong (Strontium) Bones

SKULL XRAY PATTERN APPROACH

Clinical Features

1. Bone Pain: 
1. Most common symptom.

2. Bone
1. warm
2. thickened/irregular.

3. Banana Fractures 
1. long, oblique fractures
2. common in long bones

4. Cranial foramen stenosis:
1. Compression of cranial nerves (CN 2, 3, 5, 7, 8)
• → hearing disturbances.

5. Otosclerosis:
1. Hardening of the bones in the ear,
2. causing hearing loss.

6. Thickening of the skull:
1. Frequent changes in hat size
• a classic symptom

 

• Can have lytic, blastic, or mixed phase.

Radiological Features

Important Information

• The most common mode of inheritance in osteogenesis imperfecta:
• AD.

• genetically abnormal collagen (Type I collagen defect).
• Leads to weak bones and recurrent pathological fractures.

• Type 2 is most severe

• Defects in COL1A1 or COL1A2
  (type I collagen).

Clinical Features

• Mnemonic: BITE
• Bones = fractures
• I = blue sclerae
• Teeth = imperfections
• Ear = hearing loss

• Triad:
1. Blue sclera.



• thin sclera → Choroid visible
2. Limb deformities due to recurrent fractures.
3. Deafness.

• Easy bruising.

• Multiple fractures in different stages of healing.
• On antenatal scans.
• Deformities

• Delayed dentition.

• Dental imperfections
• (dentinogenesis imperfecta → opalescent teeth that wear easily due to lack of dentin)

• Hearing loss (abnormal ossicles)

Labs

• Normal lab values.

Treatment

• Treat with bisphosphonates to ↓ fracture risk.
• Pamidronate.

• Mnemonic: Pavam koch → Pamidronate

NOTE:

• Vander Hoeve Syndrome:
• Osteogenesis Imperfecta.
• Blue sclera.
• Otosclerosis.
• Pregnant() female on shorts (Schwartz sign) vandering (Vander) in Car (Carharts), Oto (Otosclerosis) van Van (Vander)- para (Paracusis willisii)vach - bcz avalde bone(Excessive bone deposition) poyi

Marble Bone Disease / Albers-Schonberg disease

Q. An 11-month-old girl presented with pancytopenia and hepatosplenomegaly. An x-ray of her limbs showed the following picture. What is the diagnosis?

Pathophysiology

• Defect in gene for carbonic anhydrase 2
• Required by osteoclasts for acidification for bone resorption
• Decreased osteoclast function (↓ Resorption).
• Leads to increased bone formation (↑ Bone formation).
• Erlenmeyer flask deformity

• Resulting in the medullary cavity being obliterated by new bone,
• ↓↓ space for bone marrow.

Clinical Features

• Excessive thickened bone.

• Aplastic Anemia: 
• Due to marrow obliteration,
• → anemia, thrombocytopenia, and leucopenia.

• Multiple infections (due to leukopenia).

• Foramina are small
• Cranial nerve palsies

X-ray

• Bone within a bone appearance/ "Marble Bone Disease"
• Increased density of the bone.
• Mnemonic: Osteo Pettu → Bone vere bone nte ullil pettu

• Rugger Jersey Spine 



• (also seen in Renal Osteodystrophy).

• Dense, sclerotic bones.