DISORDERS OF THE BONE

by Yapa Wijeratne

Faculty of MedicineUniversity of Peradeniya Sri Lanka

1. Osteoporosis

2. Osteopetrosis (marble bone disease)

3. Paget’s disease of bone

4. Osteomalacia & rickets

5. Osteogenesis imperfacta (brittle bones)

1.Osteoporosis Relative excess of osteoclast (OC) function. A significant reduction of bone mineral density

compared with age & sex match norms. ↑ susceptibility to fractures. Disease of aging. Bone density peak at 30 yrs in both sex. Rate of bone loss is accelerated in females ,after loss

of estrogen (E2) secretion at the menopause. E2 inhibits stimulatory effect of certain cytokines which

contribute bone resorption on OC. Thereby prevent osteoporosis. At the menopause this inhibitory effect is removed & cytokines are activated.

Factors ↑ the risk of osteoporosis

1. Aging

2. Females

3. Premature menopause

4. Smoking

5. ↑ alcohol intake

6. Excessive exercise

7. Inactivity-immobilization

8. Poor [Ca+2] intake

9. Excessive caffeine intake

2. Osteopetrosis (marble bone disease)

Rare & often severe disease. characterized by increased bone density. OC are defective & unable to resorb bone in the usual

fashion. One form occurs along with renal tubular acidosis and

cerebral calcification. It is due to mutations in the gene encoding carbonic

anhydrase II (provide H+ to neutralize OH-) Narrowing & distortion of foramina → compress nerves

→neurologic defects. Crowding out of the marrow cavities →hematological

abnormalities

Histological appearance of bone in osteopetrosis

3. Paget’s disease of bone

Localized disorder characterized by accelerated bone turnover.

Initiated by ↑OC mediated bone resorption. ↑ALP activity ↑Collagen breakdown by OC result in a

↑ [Hydroxyproline] & [collagen fragments] in urine.

Histological appearance of bone in Paget’s disease of bone

4.Osteomalacia & rickets Abnormal mineralization of bone & cartilage. Vit D ↓ → defective calcification of bone matrix

Osteomalacia → adults Rickets→ children

Main defect is failure to deliver adequate amounts of [Ca+2] & [PO4

-3] to the site of mineralization.

In children , Weakness & bowing of Wt bearing bones Dental defects hypocalcemia

5. Osteogenesis imperfacta (brittle bones)

Abnormal fragility of bones Over 90% of Pt have mutations in the COLIA1,COLIA2 genes

↓Expression of collagen or structurally abnormal collagen fibrils

↓ Weakening of bone

↓ Affected infants may be bone with multiple

fractures & not survive

Radiogical appearance of the upper limbs in Osteogenesis imperfacta