Metabolic Bone Disease 1 - Metabolic Bone Disease

Anil Chopra

1.Explain the relationship between bone structure and function

2.Explain the method and indications of bone biopsy.

3.Describe the major features of osteoporosis, osteomalacia, Paget’s disease and hyperparathyroidism.

Bone has 3 main functions:

•MECHANICAL: support and site for muscle attachment

•PROTECTIVE: vital organs and bone marrow

•METABOLIC: reserve of calcium

Bone and the struts and levers it forms are adapted to resist stress, support the body and provide leverage for movement. Macroscopically it is white and dense.

Bone is composed of:

•INORGANIC - 65%

–calcium hydroxyapatite (10Ca 6PO4 OH2)

–is storehouse for 99% of Ca2+ in the body

–85% of the phosphorous, 65% Na & Mg

•ORGANIC - 35%

–bone cells and protein matrix

There are 2 main types of bone:

CORTICAL

•Generally long bones

•Make up % of skeleton

•Appendicular (make motion possible e.g. arms, legs, feet)

•80-90% calcified

•mainly mechanical and protective

CANCELLOUS

•Generally bones of Vertebrae & pelvis

•20% of skeleton

•Axial (form the head neck and trunk)

•15-25% calcified

•mainly metabolic

•Large surface

Mircoanatomy of Bones

There are 3 main types of bone cell:

»Osteoblasts - build bone by laying down osteoid

»Osteoclasts - multinucleate cells of macrophage family resorb or chew bone.

»Osteocytes - osteoblast like cells which sit in lacunae in bone.

There is constant turnover of the inorganic material in bone. This is brought about by the constant action of both osteoblasts and osteoclasts.

RANK = Receptor Activator for nuclear factor kB – this causes the maturation of osteoclast precursors when they bind to the receptor.

OPG = Osteoprotegerin –competes with RANK and therefore inhibits RANK/RANKL binding and therefore inhibits osteoclastogenesis

There are also differing types of bone based on their maturity and structure

Anatomically -Flat /long/cuboid bones: intramembranous ossification (flat) and endochondral ossification (long).

»Cancellous bone is known to have a trabecular bone structure

»Cortical bone is known to have a compact bone structure

•Wovenbone (immature): lamellae are absent. Collagen fibres are laid down in a disorganized fashion: such as states of high bone turnover.

•Lamellarbone (mature): Collagen fibres are arranged in alternating orientations allowing for the highest density of collagen per unit of tissue. This is the case of both cancellous (trabecular) and cortical (compact) bone.

Metabolic Bone Disease

This is when bone-turnover is disordered due to an imbalance of chemicals (vitamins, hormones, minerals) e.t.c. It results in reduced bone mass and density and hence can resulting in fractures from little or no trauma.

There are 3 main types of bone disease:

1. Related to endocrine abnormality (Vit D; Parathyroid hormone)

2. Non-endocrine (e.g. age related osteporosis)

3. Disuse osteopaenia.

Osteoporosis:caused primarily by age and post menopause, and secondarily by drugs and systemic disease.

Osteomalacia: a disease in which bone mineralization is defective. It can be caused by deficiencies in:

-Vitamin D

-PO4

Symptoms include:

•Sequelae

•bone pain/tenderness

•fracture

•proximal weakness

•bone deformity

Hyperparathyroidism: excess parathyroid hormone (PTH) resulting in

»increased Ca & PO4 excretion in urine

»hypercalcaemia

»hypophosphataemia

»skeletal changes of osteitis fibrosa cystica

Calcium levels are controlled by parathyroid hormone which has an effect on:

•Parathyroid glands

•Bones

•Kidneys

•Proximal small intestine

Parathyroid hormone essentially increases the levels of calcium ion in the blood by increasing the activity of osteoclasts and hence causing the thinning and lowering of bone density.

Causes:

Primary - parathyroid adenoma

- chief cell hyperplasia

Secondary - chronic renal deficiency

- vitamin D deficiency

Symptoms include

•Stones (Ca oxalate renal stones)

•Bones (osteitis fibrosa cystica, bone resorption)

•Abdominal groans (acute pancreatitis)

•Psychic moans (psychosis & depression)

Renal Osteodystrophy: characterised by skeletal changes in chronic renal disease:

  1. Increased bone resorption (osteitis fibrosa cystica)
  2. Osteomalacia
  3. Osteosclerosis
  4. Growth retardation
  5. Osteoporosis

It causes results in

-PO4 retention and hence hyperphosphataemia,

-hypocalcaemia as a result of vitamin D deficiency,

-secondary hyperparathyroidism,

-metabolic acidosis

-aluminium deposition

Paget’s Disease:

Paget’s disease is a disorder of bone turnover. It is divided into 3 stages

1. Osteolytic

2. Osteolytic-osteosclerotic

3. Quiescent osteosclerotic

Paget’s diseases rarely affects people under the age of 40 and is rarely seen in Africans and Asians. The male:female ratio is 1:1 and it affects around 3% of Caucasians over the age of 55.

-15% are mono-ostotic

- 85% are poly-ostotic

The cause of the disease is unknown but it does show a slight familial inheritance: mutation 5q35-qter - sequestosome 1 gene. Parvomyxovirus type particles have also been seen on EM in Pagetic bone.

Symptoms include:

•pain

•microfractures

•nerve compression (incl. Spinal N and cord)

•skull changes may put medulla at risk

•+/- haemodynamic changes, cardiac failure

•Development of sarcoma in area of involvement 1%