What are osteomalacia / Rickets

Osteomalacia
Disorder of mature bone in which mineralisation of new osteoid bone is inadequate or delayed

Rickets
Disease of growing bones in which defective mineralisation occurs in both bone and cartilage of epiphyseal growth plate, associated with:
Growth retardation Skeletal deformities

Rickets
The primary pathology is defective mineralisation of bone matrix The primary bone matrix mineral = hydroxyapatite = Ca10(Po4)6(OH)2 Any disease that limit the availability of calcium or phosphate will lead to rickets 2 main categories Hypocalcaemia rickets
Disorders of vitamin D metabolism or action

Hypophosphatemic rickets
Disorders of phosphate metabolism

Causes Nutritional: commonest cause in the developing countries Malabsorption Drugs that increases metabolism of vitamin D in the liver Chronic liver disease Renal rickets
Chronic renal failure RTA

Hereditary rickets
Vitamin D dependent rickets ( Type 1& 2) Vitamin D resistant rickets

Nutritional Rickets
Lack of vitamin D Commonest cause in developing countries Lack of exposure to U/ V sun light
Dark skin Covered body Kept in-door

Exclusive breast feeding

Limited intake of vitamin D fortified milk and diary products

During rapid growth

Infancy

Vitamin D dependent rickets

Type 1 Rare, autosomal recessive Lack of 1 hydroxylase enzyme Clinically and Biochemically similar to nutritional rickets except it appears early at 34 months Type 2 Rare autosomal recessive disorder 1 hydroxylase enzyme is present Lack of Calcitriol receptor Baldness

Clinical features
The earliest sign of rickets in infant is craniotabes (abnormal softness of skull) Delayed closure of anterior fontanel Widening of the forearm at the wrist (widened metaphysis= area between epiphysis and diaphysis) Rachitic rosary
Swelling of the costo-chondral junction

Harrisons groove
Lateral indentation of the chest wall at the site of attachment of diaphragm

Bowing of tibia and fibula may be observed at any age

Biochemical findings of rickets

Vitamin D deficiency rickets
Low- normal serum calcium level Increased secretion of PTH (secondary hyperparathyroidism) to compensate for low calcium Hyperparathyroidism will increase renal excretion of phosphate, leads to low serum phosphate level Elevated alkaline phosphatase enzyme Reduced urinary calcium level Low level of both 25 and 1,25- di hydroxy

 Generalized osteopenia Widening of the unmineralised epiphyseal growth plates Fraying of metaphysis of long bones Bowing of legs Pseudo-fractures (also called loozer zone)
Transverse radio lucent band, usually perpendicular to bone surface

Radiological findings of rickets

Complete fractures Features of long standing secondary hyperparathyroidism (Osteitis fibrosa cystica)
Sub-periosteal resorption of phalanges Presence of bony cyst (brown Tumor)

Therapy
Administration of vitamin D preparation
Vit D2 = ergocalciferol 25-hydroxy vitamin D = calcifedol 1 hydroxy vitamin D = one alpha 1, 25 Di hydroxy Vitamin D = Calcitriol

Calcium supplement initially in severe disease

To avoid hungry bone hypocalcaemia

Phosphate supplements in Hypophosphatemic rickets

OSTEOMALACIA
Defective mineralization of bone leading to softening of bones in adults due to def of vit d
Aetiology

COMMON IN WOMEN WITH PURDAH SYSTEM Other causes are Vitamin d undernutrition in pregnancy Malnutrition malabsorption syndrome partial gastrectomy C/F
BONE PAINS MUSCULAR WEAKNESS SPONTANEOUS FRACTURE BACKACHE TO DIFFUSE PAIN WADDLING GAIT,CARPOPEDAL SPASM AND FACIAL TWITCHING SPINE CAN LEAD TO KYPHOSIS

 Xray - diffuse rarefaction -loosers zone(radiolucent zones at sites of stress due to rapid resorption and poor mineralisation) site pubic rami, axillary border of scapula,ribs , medial cortex of femoral neck -tri radiate pelvis - protrusio acetabuli

 Bone biopsy From illiac crest confirms the diagnosis(uncalcified osteoid) BLOOD BIOCHEM serum ca and phosphates is low serum alkaline phosphatse increased TREATMENT VIT D (400IU ), HIGHER IN MALABSORPTION CALCIUM SUPPLEMENTATION TREAT UNDERLYING CAUSE

OSTEOPOROSIS Definition
A systemic skeletal disease characterized by low bone mass and micro architectural deterioration of bone tissue lead to bone fragility and susceptibility to fracture

Incidence of osteoporotic Fx
Forearm Fracture Vertebral Fracture

Hip Fracture

Diagnosis of Osteoporosis
Physical examination Measurement of bone mineral content Dual X-ray absorptiometry (DXA) Ultrasonic measurement of bone CT scan Radiography

Physical examination

Osteoporosis Height loss Body weight Kyphosis Humped back Tooth loss Skinfold thickness Grip strength

Vertebral fracture Arm span-height difference Wall-occiput distance Rib-pelvis distance

Dual X-ray absorptiometry

BMD compare with young adult female T score

Normal

< 1 SD below

>/= -1

Low bone mass ( Osteopenia )

1-2.5 SD below

< -1 > -2.5

Osteoporosis
Severe osteoporosis

>/= 2.5 SD below

>/= 2.5 SD below PLUS Fracture

</= 2.5

Assessment of fracture risk

Markers of bone turnover
Bone formation markers Alkaline phosphatase Bone isoenzyme AP Osteocalcin Procollagen propeptides of type I collagen Bone resorption markers Hydroxyproline Pyridinium crosslinks & associated peptides

Assessment of fracture risk

Predictors of low bone mass Female Advanced age Gonadal hormone deficiency ( estrogen or testosterone ) White race Low body weight & BMI Family history of osteoporosis Low calcium intake Smoking / excessive alcohol intake Low level of physical acitivity Chronic glucocorticoid use History of fracture
National Osteoporosis Foundation 1998

Available treatment
Calcium and vitamin D Hormone replacement therapy Selective estrogen receptor modulators ( SERMs ) Bisphosphonates Calcitonin Parathyroid hormone Other treatments Non-pharmacologic intervention

Vitamin D
Essential for intestinal absorption of calcium Daily recommendation 400 - 800 IU/day Esp. Low sunlight exposure, elderly, low vitamin D intake ? Decreased risk of fracture in healthy elderly with normal intake & BMD

Bisphosphonates

Benefit Potent inhibitor of bone resorption Reduce osteoclast recruitment&activity Safe Most effective Rx**

Risk Low oral bioavailability (1-3%) Food, calcium, iron, coffee, tea, orange juice decreased absorption GI discomfort Rarely - esophagitis High cost

Calcitonin
Peptide from Thyroid C cell Direct inhibition of osteoclast activity Less effective in cortical bone Salmon calcitonin nasal spray Dose 200 IU/day

Parathyroid hormone
Intermittent injection stimulate new bone formation CONTRAST to continuous infusion Teriparatide ( rhPTH[1-34] ) was approved by US-FDA for Rx of osteoporosis Transient dose-related hypercalcemia Long term effects are not known

Disorders of the Parathyroid Glands

Maintenance of calcium, phosphate and magnesium homeostasis is under the influence of two polypeptide hormones; parathyroid hormone(PTH), and calcitonin (CT), as well as a sterol hormone, 1,25 dihydroxy cholecalciferol (1,25 (OH)2D3.

Disorders of the Parathyroid Glands

These hormones regulate the flow of minerals in and out of the extracellular fluid compartments through their actions on intestine, kidneys, and bones.

Disorders of the Parathyroid Glands

The PTH acts directly on the bones and kidneys and indirectly on the intestine through its effect on the synthesis of 1,25 (OH)2D3. Its production is regulated by the concentration of serum ionized calcium. Lowering of the serum calcium levels will induce an increased rate of parathyroid hormone secretion

Disorders of the Parathyroid Glands

Calcitonin is released by the C cells (parafollicular cells in the thyroid gland) in response to small increases in plasma ionic calcium. It acts on the kidney and bones to restore the level of calcium to just below a normal set point which in turn inhibits secretion of the hormone.

Disorders of the Parathyroid Function

Hyperparathyroidism
The incidence of the disease increases dramatically after the age of 50 and it is 2-4 folds more common in women. A single adenoma occurs in about 80% of patients with primary hyperparathyroidism. Four glands hyprplasia account for 15-20% of cases. A parathyroid carcinoma could be the etiology in a rare incidence of less then 1%.

Disorders of the Parathyroid Function

Clinical Features:
In skeleton a condition called osteitis fibrosa cystica could occur with subperiosteal resorption of the distal phalanges, distal tappering of the clavicles, a salt and pepper appearance of the skull as well as bone cysts and brown tumors of the long bones. Such overt bone disease even though typical of primary hyperparathyroidism is very rarely encountered.

Disorders of the Parathyroid Function

Clinical Features: Other symptoms include muscle weakness, easy fatigability, peptic ulcer disease, pancreatitis, hypertension, gout and pseudogout as well as anemia and depression have been associated with primary hyperparathyroidism.

Diagnosis

The presence of established hypercalcaemia in more than one serum measurement accompanied by elevated immunoreactive PTH is characteristic (iPTH)

Other Diagnostic tests

Radiograph: Plain X-ray of hands can be diagnostic
showing subperiosteal

bone

resorption usually on the radial

surfacy of the distal phalanx with distal phalangeal tufting as well as cysts formation and generalzed osteopenia.

Medical Treatment of the hypercalcaemia

In acute severe forms the main stay of therapy is adequate hydration with saline and forced diuresis by diuretics to increase the urinary excretion of calcium rapidly along with sodium and prevent its reabsorption by the renal tubules.

Other agents
Calcitonin
Also inhibit osteoclast activity and prevent bone resorption

Bisphosphonates
They are given intravenously or orally to prevent bone resorption.

Other agents
Phosphate
Oral phosphate can be used as an antihypercalcaemic agent and is commonly used as a temporary measure during diagnostic workup.

Estrogen
It also decrease bone resorption and can be given to postmenopausal women with primary hyperparathyroidism using medical therapy

Surgery
Surgical treatment should be considered in all cases with established diagnosis of primary hyperparthyroidism. During surgery the surgeon identifies all four parathyroid glands (using biopsy if necessary) followed by the removal of enlarged parathyroid or 3 glands in multiple glandular disease.

What is Pagets Disease

Pagets disease of bone is a chronic disorder of the skeleton in which areas of bone undergo abnormal turnover , resulting in areas of enlarged and softened bone. or It is a disorder that involves abnormal destruction and regrowth, which results in deformity.
The disease named after SIR JAMES PAGET , the British surgeon who first described in 1877. Previously called osteitis deformans now preferred term is PAGET DISEASE.

 Normally, cells that break down old bone (osteoclasts) and cells that form new bone (osteoblasts) work in balance to maintain bone structure and integrity. Phase 1: Osteoclastic activity increases results in bone destruction.
Phase 2: Both osteoclasts and osteoblasts become overactive in some areas of bone, and the rate at which bone is broken down and rebuilt increases tremendously in involved areas. The overactive areas enlarge but, despite being large, are structurally abnormal and weak. Phase 3: Both osteoclastic and osteoblastic activity ceases the bone is sclerotic , weak and brittle

HISTOPATHOLOGY
In this picture the old bone and new bone are deposited and junction of both new and old bone show prominent cement lines , appearing as typical

mosaic

pattern pathognomonic of disease ,

the areas between the bones are fibrous from which bone has been resorbed.

age (rare < 40 years)

Many patients do not know they have Paget's disease because they have a mild case with no symptoms. Sometimes, symptoms may be confused with those of arthritis or other disorders. In other cases, the diagnosis is made only after complications have developed. Symptoms can include:

Bone pain is the most common symptom.

Bone pain can occur in any bone affected by Paget's disease. It often localizes to areas adjacent to the joints.

Headaches and hearing loss may occur when

Paget's disease affects the skull. Pressure on nerves may occur when Paget's disease affects the skull or spine.

 Increased head size, bowing of limb, or curvature of spine may occur in advanced cases.
Hip pain may occur when Paget's disease affects the pelvis or thighbone. Damage to joint cartilage may lead to osteoarthritis. Chalkstick fractures.

Hypercementosis in teeth may occur.

Large osteolytic lesion in the skull of a woman with Paget's disease

Lateral radiograph of the calvarium in a patient with paget disease reveals multiple patches of sclerotic bone in the calvarium

( cotton wool appearance)

Diagnosis
Paget's disease may be diagnosed using one or more of the following tests: Paget bone has a characteristic appearance on X-rays. A skeletal survey is therefore indicated. Bone scans are useful in determining the extent and activity of the condition. Bone biopsy. LABORATORY FEATURES Elevated urinary hydroxyproline Elevated levels of alkaline phosphatase Calcium and phosphorus usually normal

TREATMENT / MANAGEMENT
Therapy Calcitonin Oral biphosphonates Supportive braces Response to therapy Alkaline phosphatase and urinary hydroxyproline determinations.

Orthopedic surgery may be need to correct a deformity in severe cases.