Alteration of fracture healing in DIABETIC PATIENT

Normally, fracture healing proceeds with highly reproductive manner however, in severe pathological conditions such as DIABETES the progress of fracture healing can be substantially impaired.

FRACTURE HEALING

It has been described as a process of regeneration where the site of injury is replaced by bone, not scar tissue.

A cascade of events in corresponds to normal fracture healing which fulfills the three functions:-

a) Removal of debris

b) Re-establisment of the damage vascular supply

c) Restoration of the skeletal matrix

CAUSES OF IMPAIRED HEALING

absence of insulin

Insulin

Promotes marked stimulation of bone matrix and formation of cartilage.

When systemic levels of insulin are reduced, there is a late complication in nearly every body tissues, including bone.

Diabetic bone disease is characterized by OSTEOPENIA (a condition where bone mineral density is lower than normal).

Insulin can directly and indirectly action on BONE as it can:-

a) Directly increases collagen production by osteoblasts.

b) Promotes insulin-like growth factor 1 (IGF-1) which stimulates both collagen synthesis and cell proliferation in osteoblasts.

IGF-1 treatment has shown to correct osteopenia in diabetes.

Absence of insulin

Reduced calcification and ossificationà delayed cartilage formation

Fracture healing process in diabetes produce SMALLER and MECHANICALLY WEAKER callus.

metabolic alteration of calcium

Decreased systemic insulin levels à impaired duodenal calcium absorption.

This is supported by a study in humans,

Levels of calcium in the urine up to 13X than normal.

· Related to glomerular filtration, osmotic dieresis/ an insulin-dependent decrease.

Suggest that this can be offset by high calcium intake with an overall increase in food intake.

metabolic alteration of vitamin d

Vitamin D

Important for bone RESORPTION and bone FORMATION.

Synthesis of Vitamin D

Hydroxylated in liver (vitamin D3 à 25-hydroxyvitamin D3).

Metabolized in kidney to active metabolites (1,25 (OH)2 D3 and 24,25 (OH)2 D3).

alteration in vitamin d metabolism

Contributes to:-

· Osteomalacia- softening of bones due to defective bone mineralization (rickets in children)

· Osteoporosis

· Osteosclerosis- elevation in bone density; can caused by injuries that compress the bone

Because,

Vitamin D is involves with growth factors in bone formation and regulation of bone volume.

Tnf-a

During fracture healing, the levels of inflammatory molecules (TNF-a) is increased.

Diabetic animals have rapid loss of cartilage in the healing bones à increased no. of osteoclasts (regulated by TNF-a and a mediator called FOXO1).

Diabetes mediated increases in THF-a and FOXO1 may underlie the impaired healing of diabetic fractures.