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Disease Management

Defining Osteoporosis

� Classification

� Normal Bone Remodelling

� Who are at Risk?

� Diagnosis

� Analyzing the Rate of Formation or Degradation

� Lifestyle Changes To prevent Osteoporosis

� Drugs used in the treatment of Osteoporosis

� Osteoporosis Treatment Protocol

� Conclusion

With its devastating consequences including illness, pain functional limitations, reduced quality of life, loss of independence, inability to work, and even death, Osteoporosis is a serious disease.

Classification:

Osteoporosis can be classified into two main categories as follows:

 

1. Primary Osteoporosis

 

a) Idiopathic : Occurs in children and young adults where the cause is not known. Rare occurrence

 

b) Type I : Postmenopausal Osteoporosis- The cause of post menopausal osteoporosis is unknown, however the 3 most significant contributing factors are believed to be:

• Low levels of estrogen, associated with menopause, are known to accelerate bone loss in women.
  

• Insufficient amounts of calcium & vitamin D in the diet. Calcium is vital to the development & maintenance of strong bones and vitamin D is required to absorb calcium from the foods we eat.
  

• Lack of physical activity (common among many adults today) is believed to contribute to lower bone density because the skeleton is not being taxed enough to stimulate positive bone turn over

c) Type II : Senile Osteoporosis

 

2. Secondary Osteoporosis

Osteoporosis resulting from causes like chronic administration of drugs such as glucocorticoids, diseases like Cushing's syndrome, surgical procedures including bilateral oophorectomy, hystrectomy (removal of uterus). Kidney diseases and some tumours

 

Normal Bone Remodelling:

The maintenance of bone mass depends upon the metabolic activity and turnover of the skeleton, which in turn may affect the strength of bone by altering its architecture. The adult skeleton is composed of two types of bone; cortical (compact) which makes up 80% of the total bone mass and the trabecular (cancellous) which constitutes about 20%. The cortical bone predominates the skull and the shaft of the long bones. Trabecular bone on the other hand is found in the vertebrae and the distal ends of the long bone.

The process of removal of old bone and replacement with repaired new bone is a continuous process in body. this entire process is known as Bone turn over.

The whole skeletal bone turn over occurs three times in life, first turn over is from birth to first year of life. second is first year of life to skeletal maturity, and the third from adulthood till rest of life. the procedure by which this turn over occurs is known as Bone remodelling. The speed of remodelling would thus depend on the age and physiological condition of the body.

 

In the healthy adult, bone mass at skeletal maturity is neither increasing nor decreasing. There is considerable turnover of bone, of which the majority (95%) is accounted for by bone remodelling. Bone remodelling is a continuous complex process directed towards renewal and repair of the skeleton and involves resorption followed by formation. Since the bone turnover is dependent on the surface area it occurs more rapidly in the trabecular bone than the cortical.

At the start of the remodelling sequence, bone-resorbing cells (osteoclasts) migrate to or differentiate at a specific location on the bone surface to dig a cavity. After this is completed, the osteoclasts disappear; several days later, bone-forming cells (osteoblasts) are attracted principally to sites of previous resorption and infill the resorption cavity with new bone (Fig.2). The complete cycle takes about six months. Normally, except in growing bones, the rates of bone resorption and absorption are equal to each other so that the total bone mass remains constant.

Osteoporotic Bone Remodelling

The osteoporotic process may involve a disorder in the remodelling process in which resorption exceeds formation; either too much is being resorbed or too little is being formed. A decrease in bone mass is caused by an imbalance between the amount of mineral and matrix removed and subsequently incorporated into each resorption cavity, so that skeletal mass decreases progressively. In postmenopausal and may other types of Osteoporosis, the imbalance between the amount resorbed and that formed at each remodelling site is caused by a decrease in the functional capacity of osteoblasts recruited sites.

 

Who are at Risk?

The absolute risk of developing Osteoporosis depends on the individual's attainment of peak bone mass and the rate and duration of bone loss thereafter. A decreased bone mass is associated with increased risk of fracture. It has been shown that the association between bone mass and fracture risk a stronger than that between serum cholesterol and coronary events and that between systolic blood pressure and stroke-associated mortality. Such fractures are known as Fragility fractures.

 

Age

Peak bone mass is attained between the ages of 25-35. Bone mass then begins to decline. Age-related bone loss begins earlier and proceeds more rapidly in women, and there is a trend towards acceleration of bone loss after menopauses averaging 2% per year for the next 5 to 10 years followed by a slower rate of bone loss. Lifetime losses may reach 30 to 40% of peak bone mass in women and 20 to 30% in men.

 

The risk factors for Osteoporosis are as follows:

 

Individual Characteristics

• Caucasian race or Asian ethnicity

• Menopause

• Family history of Osteoporosis

• Low bone mass

• Low body weight- Small-boned and thin women (under 127 pounds) are at greater risk. ( compared to obese women who are protected due to conversion of some hormones into anabolic hormones by the fat tissue).

• Small stature

Lifestyle

• Cigarette smoking

• Alcohol abuse

• Sedentary lifestyle

• Inadequate calcium intake

• Vitamin D deficiency

• Excessive caffeine

• Excessive exercise

Drug Use

• Corticosteroids/glucocorticoids

• Gonadotropin-releasing hormones

• Anticonvulsants (Phenobarbital/phenytoin)

• Heparin

For many people, these are life-saving or life-enhancing drugs, and their use may be the only way to achieve a better quality of life.

 

Secondary Causes

• Cushing's syndrome

• Anorexia nervosa

• Mal absorption syndromes.

• Hyperprolactinemia

• Multiple myeloma

• Hyperparathyroidism.

• chromic Renal failures or repeated dialysis

• Rheumatoid Arthritis

• Fragillitus oseum (in kids.)

• Pagets disease.

Surgical Procedures

• Bilateral oophorectomy

• Gastrectomy

• Hystrectomy

Diagnosis:

Osteoporosis is a silent disease in its initial stages and a careful interpretation of the clinical evaluation is essential while diagnosing the disease. Clinical evaluation should include both the history and the physical examination. The disease runs long enough before symptoms appear, hence it should be looked for if there is a reason to suspect.

 

A postmenopausal woman, with low back pain, a thin body frame, sedentary life style and a family history of the disease is a sure candidate for Osteoporosis. The several risk factors and the disease contributing to Osteoporosis should be taken into consideration while evaluating a case of Osteoporosis.

 

Conventional X-ray is relatively insensitive and bone loss is apparent only when the bone mass has decreased by 30-50%. Bone biopsies also play a role in the study of Osteoporosis. Recently, however, the advances in methods to diagnose Osteoporosis and assess the risk of future fractures have been dramatic. Non-invasive measurements of bone mineral density using bone densitometers allow skeletal integrity, both centrally and peripherally, to be assessed with an accuracy exceeding 95% and a precision doses.' The various bone densitometers available are DEXA-Dual Energy X- ray Absorptiometry, pDEXA - peripheral DEXA, SXA - Single X-ray Absorptiometry, RA - Radiographic Absorptiometry, QCT-Quantitative Computer Tomography. Lately Ultrasonic bone densitometer has been introduced which is safer than other densitometers since it does not involve ionizing radiations, but has a lower accuracy.

 

DEXA is still the 'Gold Standard' for measuring bone density. The results of the densitometers are interpreted in terms of T-scores. describes the bone mass of the patient compared to the mean peak bone mass of the normal young adult reference population using standard deviation.

 

The only Orthopaedic condition recognised by W>H>O as public health hazard is Osteoporosis.

The World Health Organization defines Osteoporosis using T-scores as follow:

 

(BDM = Bone mineral density SD = Standard deviation)

 

Analyzing the Rate of Formation or Degradation:

The rate of formation or degradation of the bone matrix can be assessed either:

• By measuring a prominent enzymatic activity of the bone forming or resorbing cells such as alkaline phosphatase etc.
  

• By measuring bone matrix components released into circulation during formation or resorption.

The use of sensitive biochemical markers is gaining clinical importance. The potential uses of biochemical markers are to assess the rate of bone turnover, to monitor biochemical effects of therapy and to help evaluate patient compliance to therapy. Pyridinoline and deoxypyridinoline cross-links are currently considered 'Gold Standard' in the assessment of bone resorption. In Osteoporosis, the bone turnover is increased resulting in an increase in markers of bone formation and bone resorption.

 

The following table shows the biochemical markers used in current practice:

 

Lifestyle Changes To prevent Osteoporosis:

The dictum of medically healthy life is " IF YOU DO NOT USE IT YOU LOSE IT" Hence use of bone needs pulling of structures attached on it i.e. the muscles and tendons. so regular exercise grounds its importance.

 

Building strong bones, especially before the age of 30, can be the best defense against developing osteoporosis, and a healthy lifestyle can be critically important for keeping bones strong.

• Make exercise or physical activity a part of your day-The best exercise for your bones is weight-bearing exercise such as walking, dancing, jogging, stair-climbing, racquet sports and hiking. If you have been sedentary most of your adult life, be sure to check with your healthcare provider before beginning any exercise program.
  
  
  
  

• Bones react to load by gradually growing stronger & denser.
  Recent studies have shown that the risk of osteoporosis is lower for people who are active, and especially those who do load-bearing, or weight-bearing activities at least three times a week. The best exercises are weight-lifting, jogging, hiking, stair-climbing, step aerobics, dancing, racquet sports, and other activities that require your muscles to work against gravity. Swimming and simply walking, although good for cardiovascular fitness, are not the best exercises for building bone. Thirty minutes of weight-bearing exercise daily benefits not only your bones, but improves heart health, muscle strength, coordination, and balance. Those 30 minutes don't need to be done all at once; it's just as good for you to do 10 minutes at a time. Log on to http://ag.arizona.edu/maricopa/fcs/bb/bbchart.htm, to check out the bone building exercise chart for beginners, intermediate and advanced trainers.
  
  
  
  

• Quit smoking and reduce your risk for osteoporosis & most other diseases.
  

• Reduce soft drink consumption. The phosphorus in soft drinks appears to have a deleterious effect on bone tissue. Colas & beverages with caffeine & phosphorus appear to cause bone resorption (problem for children & adults).
  

• Alcohol consumption under control

• Be sure to get your daily dose of calcium and vitamin D, both nutrients are necessary to build & maintain bone tissue. The recommended does for postmenopausal women below 65 years of age is 1000 mg/day and 1500 mg/day above 65 years of age. Vitamin D is needed for the body to absorb calcium. Without enough vitamin D, you will be unable to absorb calcium from the foods you eat, and your body will have to take calcium from your bones. Vitamin D comes from two sources: through the skin following direct exposure to sunlight and from the diet. Experts recommend a daily intake between 400 and 800 IU per day, which also can be obtained from fortified dairy products, egg yolks, saltwater fish and liver.
  For sources of calcium in diet click here.

• See your doctor for a Bone Mineral Density Test, after age 50. A Bone Mineral Density test (BMD) is the only way to diagnose osteoporosis and determine your risk for future fracture. Since osteoporosis can develop undetected for decades until a fracture occurs, early diagnosis is important.

Drugs used in the treatment of Osteoporosis:

Drugs used in the treatment and prevention of Osteoporosis are traditionally classified as antiresorptive and anabolic. The majority of those currently licensed, fall into the former category. The predominant effect of antiresorptive agents is to prevent bone loss, although small increases in bone mass may occur. Hormone replacement therapy, calcitonin and bisphosphonates are the major antiresorptive drugs used. Anabolic drugs like Anabolic steroids on the other hand have the potential to increase bone mass.

 

Sodium flouride in high doses spoils the bones but in small doses it acts as bone hardener. It also has an anabolic action. Its medical use is debatable. Calcitonin now can be given as nasal spray (MIACALCIC) Parathyroid hormone also is anabolic in small doses.

 

HRT:

Estrogen is believed to act directly on bone cells through high affinity estrogen receptors expressed by osteoblasts. Though the exact mechanism is still not known, estrogen is believed to inhibit bone resorption. HRT and estrogen replacement therapy (ERT) have been approved by the FDA for the prevention and, for some products, management of osteoporosis. There are side effects of oestrogens. see below.

 

However the research is now directed to find chemical compounds which would have action like that of oestrogen but, they would act only on bones etc. they are known as S.E.R.M.

Raloxifene (Brand name: Evista�) is a selective estrogen receptor modulator (SERM)approved by the FDA for both prevention and treatment of osteoporosis in postmenopausal women.

However, HRT has several contraindications e.g.. breast or endometrial tumors, uncontrolled hypertension, chronic or acute hepatic diseases, recent thromboembolic, cardiovascular or coronary artery disease, endometriosis, uterine myelomas, etc. Short term adverse effects of hormone replacement therapy include vaginal bleeding, breast tenderness and upper gastrointestinal symptoms.

 

Calcitonin

Calcitonin primarily inhibits bone resportion by inhibiting osteoclast function as well as by reducing osteoclast number. It is FDA-approved for the treatment of osteoporosis in women who are at least 5 years postmenopausal. It is delivered as a single daily intranasal spray and subcutaneous administration by injection also is available.

 

Bisphosphonates

Bisphosphonates are synthetic, non-biodegradable analogues of pyrophosphate which inhibit bone resorption. Etidronate is the first generation bisphosphonate used to treat Osteoporosis. Its propensity to inhibit mineralization however limits its use and necessitates its cyclic administration.

Alendronate is a third generation bisphosphonate and the first non-hormonal therapy approved by the U.S. FDA for the treatment and prevention of Osteoporosis. In vivo studies indicate that Alendronate is 1000 times more potent than etidronate.

 

Various clinical trials have shown that daily treatment with Alendronate 10 mg progressively increases bone mass in the spine, hip, and total body and reduce the incidence of vertebral and nonvertebral fractures and height loss in postmenopausal women with Osteoporosis. The low incidence of side effects and good tolerability of Alendronate is also evident from these studies. Thus Alendronate fulfills the ultimate goal of Osteoporosis management which is the reduction in the incidence of fractures. Alendronate is now available in single weekly doses. Its effect appears in some months, Hence the drug should as a rule be started the day menopausal symptoms start knocking the door.

 

Pamidronate the new compound is under trial and may prove more promising.

 

Osteoporosis Treatment Protocol:

Conclusion:

Although much remains to be learned about the causes and management of Osteoporosis, the constant research in this field is giving clinicians a wider range of therapeutic options. Women interested in bone health, whether or not they are postmenopausal, should practice bone-healthy behaviors. It is important to get the daily-recommended dosage of calcium and vitamin D; engage in regular weight-bearing exercise; avoid smoking and excessive alcohol. Most important of all: women need to know their own family-health history and discuss treatment options regularly with their health care professional.

Related Links

• Managing Osteoporosis through yoga

• Rising Against Osteoporosis

• 7 scary truths about your bones

• Reduce the Osteoporosis risk by Weight bearing exercises