Osteoporosis is becoming increasingly common in clinical practice. It is a skeletal disorder characterised by reduction in bone mass / unit volume with accompanying microarchitectural damage that increases bone fragility and the risk of fractures. Osteoporosis leads to reduction in absolute bone mass with a normal ratio of unmineralised to mineralised bone matrix. Histologically the cortices are thinned and porous and the trabeculae are fewer, thinner and less connected.
The incidence of osteoporosis increases with age, becoming widely prevalent in the elderly. Osteoporosis is a growing public health problem as longevity of the population is increasing. It gains significance as a health hazard due to increased risk of fracture. The most common fractures are in the thoracic and lumbar vertebral bodies (crush or wedge fractures), the neck and intertrochantric regions of the femur (hip fractures) and the distal radius (Colle’s fractures), but fractures of any bone is possible.
Types of Osteoporosis
Osteoporosis has been divided into primary and secondary depending on whether or not a patient has a recognisable disease or using a drug that can cause bone loss. The primary form of the disease is the most common type.
Primary or involutional osteoporosis
More than 80% of osteoporosis occur among post menopausal and aging populations. Fracture risk at any age is determined by skeletal mass, which depends on the maximum bone mass achieved, and on the subsequent rate of bone loss. In addition, factors predisposing to falls reduced bone elasticity and decreased dissipation of force over bone by muscle and less coordinated muscle contractions also add to fracture risk.
Determinants of maximum bone mass
Peak bone mass occurs at approximately 20-25 years of age. After 4th decade bone is progressively lost. Peak bone mass is primarily determined genetically as a function of gender and body size. In addition vitamin D through a highly specific vitamin D receptor in the bone has a role to play. Adequate calcium nutrition and exercise also increase the bone mass.
Determinants and pathogenesis of bone loss
In the adult skeleton after the peak bone mass is acquired, remodeling dominates to keep the bone dynaemic and elastic and to maintain adequate sources of calcium. This is accomplished by remodeling units, which are composed of osteoclasts and osteoblasts. Bone remodeling units are coupled by cytokines. Maintenance of a coupled remodeling unit permits bone mineral density to remain relatively constant. By the 4th or 5th decade, age related bone loss occurs in both sexes due to excess bone resorption over bone formation. This could result from a defect in the osteoblast or in the body’s ability to recruit them or from a hyperactivity or overrecruitment of osteoclasts. Thus the net loss of bone is a universal aging process though rates of bones loss appears to be determined by genetic, endocrine and environmental factors.
|Genetic factors||Environmental factor||Endocrine factors|
|White or Asian race||Low calcium and Vitamin D||Female sex|
|Positive family history||Sedentary life style||Early menopause|
|Small body build||Alcohol abuse||Late menarche|
|Certain Vitamin D receptor alleles||Cigarette smoking|
|Type I||Type II|
|Sex F : M||6:1||2:1|
|Type of bone loss||Mainly trabecular||Trabecular and cortical|
|Rate of bone loss||Accelerated||Not accelerated|
|Major fracture sites||Vertebrae and distal radius||Vertebrae and hip|
Type I: Postmenopausal osteoporosis
Oestrogen inhibits factors such as inteleukins and tumor necrosisfactor, which enhance bone resorption. It enhances factors such as transforming growth factor and insulin like growth factor which stimulate bone formation. Oestrogen deficiency leads to increased turnover and to a greater increase in bone resorption than bone formation. These in turn decrease paratharmone secretion and 1,25 dihydroxycholecalciferol production. Hence calcium absorption is reduced. Fractures occur at sites that contain relatively large amount of trabecular mass such as vertebral body, distal forearm, ankle, mandible and maxilla. Vertebral fracturesare crush or collapse type and usually associated with >25% reduction invertebral height. It occurs mainly in women between 50 to 65 years.
Type II Osteoporosis
Occurs in both men and women above 70 years. Fractures occur at sites, which contain both trabecular (25-50%), and cortical bone. Fracture hip and proximal humerus are the common sites. Gradual and progressive deformities of vertebrae occur leading to dorsal kyphosis. Anterior wedge fractures of vertebrae are common. Paratharmone levels are increased. Here rate of bone formation is reduced.
Evaluation of primary osteoporosis
Estimation of bone mineral density
There are several sensitive noninvasive methods for measuring bone density
- Dual energy xray absorptiometry
- Single photon absorptiometry
- Dual photon absorptiometry
- Quantitative computed tomography
- Ultrasound transmission velocity
Among them dual energy xray absorptiometry is the most precise method. A single bone mass measurement has far greater predictive value regarding fracture risk. Risk of fractures increases two fold for every one standard deviation decrease in bone density.
Biochemical markers of bone turnover
They provide information on bone formation and bone resorption dynaemics.They are used for screening and diagnostic purposes, evaluating treat mentregimes and monitoring theraputic effects. Markers of bone turnover are classified into markers of bone formation and markers of bone resorption.
Markers of bone formation
- Serum osteocalcin
- Total and bone-specific alkaline phosphatase
- Procollagen peptides
Among these serum osteocalcin is the most sensitive index of bone formation and it is increased in conditions with high bone turnover.
Markers of bone resorption
- Tartrate-resistant acid phosphatase
- Free pyridinoline and deoxypyridinoline and type I collagen telopeptides breakdown products
- Urinary pyridinoline and deoxypyridinoline and type I collagen telopeptides breakdown products
- Fasting urinary calcium and hydroxyproline
Urinary hydroxy pyridinium cross links: Pyridinoline and deoxypyridinoline are released when mature collagen is broken down and are excreted in urine. These compounds are the most specific and sensitive markers of bone resorption. Type I collagen telopeptide breakdown products are also sensitive markers.
Management of osteoporosis include prevention of bone loss in the high risk group and treatment of established osteoporosis. Treatment modalities include calcium and vitamin D supplementation, oestrogen, bisphosphonateand growth factors. These agents either are anti resorptive or increase bone formation. Thus awareness of the risk of age related bone loss and effective implementation of preventive measures and early management of established osteoporosis will prevent fractures and the resultant complications.
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Dr.Vijaya Ganapathy MD, DM
E-Mail :[email protected]