Osteoporosis and osteomalacia

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Control of serum calcium levels
Bone is made up of hydroyapatite and a fibrous framework.

Ca3(PO4)2 + Ca(OH)2 à Ca5(PO4)3(OH)
Tricalcium phosphate + calcium hydroxide à hydroxyapatite

Bone is maintained by osteoClasts which ‘Crush’/breaks down bone and osteoBlasts which Build bone. The breaking down of old bone is also called bone resorption and the formation of new bone is called ossification. This constant relaying of bone helps reshape bones, and repair micro-damages as well as injuries. This continuous bone remodeling is called bone turnover. In adults the rates of bone formation and bone breakdown is usually almost equal.

Calcium levels in the body are regulated by parathyroid hormone, calcitonin and vitamin D. The levels of calcium in blood is carefully controlled in the short term, and the total levels of calcium in the body also needs to be constantly maintained. The regulation of calcium is mainly carried out by Parathyroid hormone, which acts on the bone, the kidneys and indirectly the gut. Vitamin D is also needed to control the absorption of calcium. (see calcium regulation)


Osteoporosis
Osteoporosis refers to the loss of bone tissue and density leading to brittle bones which are liable to fracture. [ossis- bone / porosis – porus in] The WHO defines osteoporosis as a bone density of -2.5 standard deviations away from the mean bone density of healthy young adults. Osteoporosis leads to higher rates of fractures which is a major cause of morbidity and mortality in the elderly.

There are many risk factors leading to osteoporosis, including certain genes, nutritional factors, and physical activity. However, estrogen deficiency and vitamin D insufficiency are the most common causes. Estrogen has a protective effect on bones and helps indirectly inhibit the numbers of both osteoclasts and osteoblasts. The exact mechanisms of this are not known. During menopause, the levels of oestrogen drops, rapidly increasing bone turnover. Bone resorption rates also increase greatly leading to accelerated bone loss, and eventually osteoporosis.

Risk factors of osteoporosis
Factors leading to bone loss
Risk factors for fractures
Factors affecting peak mass
Genetical factors: collagen type 1A1
Vitamin D receptor
Oestrogen receptor genes
Nutritional factors
Sex hormone status
Physical activity
Hyperparathyroidism
Hyperthyroidism
Malabsorption
Vitamin D insufficiency
Previous fractures
Age
Glucocorticoid therapy
Smoking
falls

Investigations
Dual energy X- ray absoptiometry measures mineral per surface area using low doses of radiation. This is the gold standard for bone density measurements
Quantitative ultrasound and CT scanning can also be used to measure bone density.

Prevention and treatment
Non pharmacological
l          Managing fractures
l          Calcium and vitamin D supplement
l          Exercise
l          Smoking cessation
l          Reduce falls via physiotherapy, assessment of homes, and hip protectors
Pharmacological
Alendronate, risedronate, ibandronate, zoledronate, raloxifene, hormone replacement therapy, strontium ranelate, teriparatide, human recombinant parathyroid hormone 1-84 and combined calcium and vitamin D regiments have been shown to be effective in reducing fractures.

Biphosphonates and strontium ranelate are considered first line drugs due to their efficacy at reducing spine and hip fractures, the most common sites for fractures in osteoporosis. Biphosphonates adhere to hyroxyapatite and inhibit osteoclasts. They include alendronate, risedronate, and zoledronate.

Strontium ranelate
Made up of 2 strontium atoms joined to ranelic acid. The mechanisms of this is not known, but it has weak anti-resorptive activity and maintains bone formation.

Osteomalacia

Osteomalacia is the softening of bones due to inadequate mineralization. It is the adult counterpart to rickets. Osteomalacia is commonly caused by vitamin D deficiency and may also be caused by calcium deficiency, or defects affecting vitamin D metabolism.

As vitamin D is mainly obtained from the diet and from sunlight, vitamin D deficiencies can be caused by an inadequacy of either of these. (see calcium regulation) Certain gastrointestinal diseases also affect vitamin D absorption including coeliac disease and small intestinal chron’s disease. As vitamin D also needs to be activated by the kidney and liver, diseases in these parts of the body can also affect vitamin D levels leading to osteomalacia.

When a patient is deprived of vitamin D, the total calcium levels of the body drop over a long period of time. As the body cant replenish its serum calcium levels from the diet, it continuously secretes parathyroid hormone, breaking down bone to supply calcium. This therefore leads to osteomalacia.

Symptoms
Osteomalacia usually leads to bone and muscle pain and fractures.

Investigations
Serum alkaline phosphatase: alkaline phosphatase is a marker of osteoblastic activity. Alkaline phosphatase levels will be high due to increased osteoblastic activity.
Plasma calcium: normal, but may be low in severe cases
Serum phosphate: may be slightly low due to PTH induced excretion of phosphates, but may also be normal.
Serum 25OHD (form of vitamin D): often low.

Treatment
Vitamin D, calcium of phosphorus supplements are often prescribed. People with problems with absorption or the liver may benefit from higher doses. Calcitriol may also be prescribed if the kidneys are unable to effectively hydroxylate vitamin D. 

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