- Introduction
- Pathophysiology
- Treatment
- Prevention
Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures of the hip, spine, and wrist. Men as well as women suffer from osteoporosis, a disease that can be prevented and treated. Osteoporosis is a “silent” risk factor as hypertension is a risk factor to stroke.
Facts and Figures
Osteoporosis is a major public health threat for 28 million Americans, 80% of whom are women.
In the U.S. today, 10 million individuals already have osteoporosis and million more have low bone mass, placing them at increased riisk for this disease.
One out of every two women and one in eight men over 50 will have an osteoporosis-related fracture in their lifetime.
More than 2 million American men suffer from osteoporosis, and millions more are at risk. Each year, 80,000 men suffer a hip fracture and one-third of these men die within a year.
Osteoporosis can strike at any age.
Osteoporosis is responsible for more than 1.5 million fractures annually, including 300,000 hip fractures, and approximately 700,000 vertebral fractures, 250,000 wrist fractures, and more than 300,000 fractures at other sites.
Estimated national direct expenditures (hospitals and nursing homes) for osteoporosis and related fractures is $14 billion each year.
Though this data is American, we as Indians are at the same amount of risk and lack of record keeping prevents us from giving out these accurate figures. The magnitude of problems treated to osteoporosis in the Indian Scenario is almost the same or probably slightly worse compared to the American scenario.
Medical Impact
Fractures and their complications are the relevant clinical sequelae of osteoporosis. The most common fractures are those of the proximal femur (hip),vertebrae (spine), and distal forearm (wrist), but because osteoporosis is a systemic disease causing bone loss throughout the skeleton, almost all fractures in older adults are due in part to low bone density. These common fractures may be followed by full recovery or by chronic pain, disability, and even death.
The most serious outcome of osteoporosis is hip fracture, which can result in up to 10% to 20% excess mortality within 1 year. Additionally, up to 25% of hip fracture patients may require long-term nursing home care, and only a third fully regain their prefracture level of independence.
Vertebral fractures also cause significant complications including back pain, height loss, and kyphosis. Postural and height changes associated with kyphosis may limit activity, including bending and reaching, and their cosmetic effects may erode self-esteem. Multiple thoracic fractures may result in restrictive lung disease, and lumbar fractures may alter abdominal anatomy, leading to constipation, abdominal pain, distention, reduced appetite, and premature satiety.
Hip and vertebral fractures can also cause psychological symptoms, most notably depression, as patients grapple with pain, physical limitation, and lifestyle. Anxiety, fear, and anger may also impede recovery. The high morbidity and consequent dependency associated with these fractures strain interpersonal relationships and social roles for patients and their families.
In developing these recommendations, the NOF has considered the entire range of potential fracture outcomes.
Economic Toll
The economic considerations given below are for the American Healthcare System. Our healthcare system is already undergoing a change due to the entry of private companies in the insurance sector. This example is to highlight the problems we would soon face.
Osteoporotic fractures create a heavy economic burden. In 1995, they were the presumed cause of 432,000 hospital admissions, almost 2.5 million physician visits, and about 180,000 nursing home admissions in the United States that year.
Direct medical expenditures alone for osteoporotic fractures in that year were estimated at $13.8 billion. These costs are anticipated to rise along with the growing elderly population. Hip fractures incur the greatest osteoporosis-related health care expenditures. By one estimate, the number of hip fractures and their associated costs could more than triple by the year 2040.
Pathophysiology
Bone is living, growing tissue. It is made mostly of collagen, a protein that provides a soft framework, and calcium phosphate, a mineral that adds strength and hardens the framework. This combination of collagen and calcium makes bone strong yet flexible to withstand stress. More than 99% of the body’s calcium is contained in the bones and teeth. The remaining 1% is found in the blood.
Throughout your lifetime, old bone is removed (resorption) and new bone is added to the skeleton (formation). During childhood and teenage years, new bone is added faster than old bone is removed. As a result, bones become larger, heavier, and denser. Bone formation continues at a pace faster than resorption until peak bone mass (maximum bone density and strength) is reached during the mid-20s. After age 30, bone resorption slowly begins to exceed bone formation. Bone loss is most rapid in the first few years after menopause but persists into the postmenopausal years.
Osteoporosis develops when bone resorption occurs too quickly or if replacement occurs too slowly.
The process of bone remodeling that maintains a healthy skeleton is a kind of preventive maintenance program, continually removing older bone and replacing it with new bone. The remodeling process also serves metabolic needs for calcium. Bone loss occurs when the balance between bone removal and replacement is altered, causing less bone to be replaced than was removed. The consequence is reduced bone mass and an increase in fracture risk.
It is very important here to distinguish between the terms “Osteomalcia” and ”Osteoporosis”. Osteomalacia is due to abnormalities of calcium and vitamin D metabolism and the bone formed under these conditions is of poor quality. In osteoporosis the bone quality is good but the quantity is not sufficient, the calcium and vitamin D metabolism in these cases may be intact. We also have seen severe vitamin D deficiency in elderly osteoporotic patients and therefore osteomalacia and osteoporosis can co-exist. Osteomalacia before skeletal maturity is termed as “Rickets”. Osteopenia on the other hand is a term used by radiologists to describe the features of osteomalacia.
Classification
Osteoporosis has been classified as primary osteoporosis and secondary osteoporosis. Primary Osteoporosis is further classified as Type I or post-menopausal type and Type II or senile osteoporosis. Secondary osteoporosis as the name suggests is osteoporosis due to side effects of drugs like corticosteroids or due to the effects of prolonged immobilization.
Type I osteoporosis is characterized by wrist and vertebral fracture and typically occurs in young (45 to 65 years) patients whereas type II osteoporosis is characterized by hip fractures and is seen in elderly (> 65 years) patients. Reduced gonadal function (estrogen) is blamed for Type I osteoporosis whereas age related bone loss is the cause for type II osteoporosis. In Type I the bone loss occurs mainly in the trabecular compartment whereas in type II bone loss involves cortical bone.
The skeleton can be divided into two main compartments and types of bone
Axial skeleton : This refers to the spine and vertebrae. The bone in this region is primarily cancellous or trabecular.
Appendicular skeleton : This refers to the long bones of the arms and legs. The bone in these areas is primarily compact or cortical.
At the end of the long bones, there is a variable regional combination of trabecular and cortical bone. For example, the ultra-distal radius (1.5 cm proximal to the styloid process) consists of approximately 25% cortical bone and 75% trabecular bone, the midshaft of the radius (measured at two thirds from the olecranon to the styloid process) is 90%cortical bone. A similar variable composition is noted in:
- The femoral neck
- The greater trochanter
- The shaft of the femur
Because of the anatomic variability in these compartments, bone loss occurs more rapidly in trabecular bone increasing its vulnerability to fracture. This explains why osteoporotic fractures tend to occur in:
- The vertebrae
- The femoral neck
- At the ends of the long bones.
DISEASES : few examples
- Ankylosing spondylitis
- Chronic obstructive pulmonary disease
- Endometriosis
- Epidermolysis bullosa
- Hemophilia
- Insulin-dependent diabetes mellitus
- Lymphoma and leukemia
- Malabsorption syndrome
- Nutritional disorders
- Osteogenesis imperfecta
- Pernicious anemia
- Rheumatoid arthritis
- Sarcoidosis
- Severe liver disease, especially primary biliary cirrhosis
- Anticonvulsants
- Cigarette smoking
- Cytotoxic drugs
- Excessive alcohol
Certain factors are linked to the development of osteoporosis or contribute to an individual’s likelihood of developing the disease. These are called “risk factors.” Many people with osteoporosis have several of these risk factors, but others who develop osteoporosis have no identified risk factors. There are some risk factors that you cannot change, and others that you can:
Risk factors you cannot change
Gender : Your chances of developing osteoporosis are greater if you are a woman. Women have less bone tissue and lose bone more rapidly than men because of the changes involved in menopause.
Age : the older you are, the greater your risk of osteoporosis. Your bones become less dense and weaker as you age.
Body size : Small, thin-boned women are at greater risk.
Ethnicity : Caucasian and Asian women are at highest risk.
African-American and Latino women have a lower but significant risk.
Family history : Susceptibility to fracture may be, in part, hereditary. People whose parents have a history of fractures also seem to have reduced bone mass and may be at risk for fractures.
Risk factors you can change
- Sex hormones : abnormal absence of menstrual periods (amenorrhea), low estrogen level (menopause), and low testosterone level in men.
- Anorexia.
- A lifetime diet low in calcium and vitamin D.
- Use of certain medications, such as glucocorticoids or some anticonvulsants.
- An inactive lifestyle or extended bed rest.
- Cigarette smoking.
- Excessive use of alcohol.
Osteoporosis is often called the “silent disease” because bone loss occurs without symptoms. People may not know that they have osteoporosis until their bones become so weak that a sudden strain, bump, or fall causes a fracture or a vertebra to collapse.
Collapsed vertebrae may initially be felt or seen in the form of severe back pain, loss of height, or spinal deformities such as kyphosis or stooped posture.
Detection
Following a comprehensive medical assessment, your doctor may recommend that you have your bone mass measured. Bone mineral density (BMD) fractures due to osteoporosis), while others measure bone in the heel or hand. These tests are painless, noninvasive, and safe. Bone density tests can:
Detect low bone density before a fracture occurs.
Confirm a diagnosis of osteoporosis if you have already fractured.
Predict your chances of fracturing in the future.
Determine your rate of bone loss and/or monitor the effects of treatment if the test is conducted at intervals of a year or more.
Treatment
A comprehensive osteoporosis treatment program includes a focus on
- Prevention : proper nutrition, exercise, and safety issues to prevent falls that may result in fractures.
- Therapeutic : This includes medicines which may be prescribed to slow or stop bone loss, increase bone density, and reduce fracture risk.
Nutrition
The foods we eat contain a variety of vitamins, minerals, and other important nutrients that help keep our bodies healthy. All of these nutrients are needed in a balanced proportion. In particular, calcium and vitamin D are needed for strong bones as well as for heart, muscles, and nerves to function properly. Green leafy vegetables like methi and palak (spinach) not only provide calcium but also are rich in Vitamin K, which also is essential in treatment. Indian diets are generally deficient in calcium mainly because milk in our country is not fortified as in other countries and the vegetarian diet as such provides very minimal calcium if milk and milk related products are excluded. Lactose intolarance is very common in Indian patients which does create a problem in balancing the diet for such patients.
Exercise
Exercise is an important component of an osteoporosis prevention and treatment program. Exercise not only improves your bone health, but it increases muscle strength, coordination, and balance and leads to better overall health. While exercise is good for someone with osteoporosis, it should not put any sudden or excessive strain on your bones. Patients recovering from vertebral fractures experience a lot of pain in the back extensors. A good rehab programme gets these patients out of bed fairly rapidly. Exercises have to be prescribed depending on the need of every individual patient and it is important to note that many geriatric patients have other orthopaedic problems like osteoarthrosis of the knees or a degenerative disc disease. Anti-gravity exercises are more important for the bones and stair climibing, brisk walking is one of the simplest exercises that one can do. For upper extremities simple dumbbell exercises are very good.
Fall Prevention
Accicental falls is a special concern for men and women with osteoporosis. Falls can increase the likelihood of fracturing a bone in the hip, wrist, spine or other part of the skeleton. It is hardly surprising that 60% falls are sustained at home by our elderly population. Attention to some very small details at home can prevent these falls. In addition to the environmental factors listed below, falls can also be caused by impaired vision and/or balance, chronic diseases that impair mental or physical functioning, and certain medications, such as sedatives and antidepressants.
It is important that individuals with osteoporosis be aware of any physical changes they may be experiencing that affect their balance or gait, and that they discuss these changes with their health care provider.
Some tips to help eliminate the environmental factors that lead to falls include:
Outdoors : Use a cane or walker for added stability; wear rubber-soled shoes for traction; walk on grass when sidewalks are slippery; be careful on highly polished floors that become slick and dangerous when wet. Use plastic or carpet runners when possible.
Indoors : Keep rooms free of clutter, especially on floors; keep floor surfaces
smooth but not slippery; wear supportive, low-healed shoes even at home; avoid walking in socks, stockings, or slippers; be sure carpets and area rugs have skid-proof backing or are tacked to the floor; be sure stairwells are well lit and that stairs have handrails on both sides; install grab bars on bathroom walls near tub, shower, and toilet; use a rubber bath mat in shower or tub; keep a flashlight with fresh batteries beside your bed; if using a step stool for hard to reach areas, use a sturdy one with a handrail and wide steps; add ceiling fixtures to rooms lit by lamps.
Consider purchasing a cordless phone so that one does not have to rush to answer the phone when it rings or you can call for help if you do fall.
The Therapeutic Role of Medication
Pharmacotherapy is started in all women with BMD T-scores below -2 in the absence of risk factors and in women with T-scores below 1.5 if other risk factors are present. Women above 70 years with multiple risk factors are at high enough risk of fracture and should start therapy without BMD measurements.
Adequate intake of calcium and Vitamin D are an absolute must. The daily recommended calcium requirement is 1200 mg of calcium and 400 to 800 IU of Vitamin D. The daily intake in the Indian population varies from as low as 200 to 700 mg. Details of the patient’s diet are therefore very important before you prescribe calcium containing preparations. Fortifying milk with Vitamin D should be made compulsory by the government of India. This requires passing a legislation. The cheapest available calcium is the calcium carbonate salt but it can have unpleasant side effects like constipation. Calcium citrate is the recommended compound and is available in India freely.
Estrogen
Estrogen replacement therapy (ERT) has been shown to reduce bone loss, increase bone density in both the spine and hip, and reduce the risk of hip and spinal fractures in postmenopausal women. ERT is administered most commonly in the form of a pill or skin patch and is effective even when started after age 70. When estrogen is taken alone, it can increase a woman’s risk of developing cancer of the uterine lining (endometrial cancer). To eliminate this risk, physicians prescribe the hormone progestin in combination with estrogen (hormone replacement therapy or HRT) for those women who have not had a hysterectomy. ERT/HRT relieves menopause symptoms and has been shown to have beneficial effects on both the skeleton and heart.
Experts recommend ERT for women at high risk for osteoporosis. ERT is approved for both the prevention and treatment of osteoporosis. ERT is especially recommended for women whose ovaries were removed before age 50. Estrogen replacement should also be considered by women who have experienced natural menopause and have multiple osteoporosis risk factors, such as early menopause, family history of osteoporosis, or below normal bone mass for their age. As with all drugs, the decision to use estrogen should be made after discussing the benefits and risks and your own situation with your doctor. The other benefits of ERT are cardioprotection and decrease in the postmenopausal symptoms like hot flushes etc.
Raloxifene : Raloxifene is a drug that is approved for the prevention and treatment of osteoporosis. It is from a new class of drugs called Selective Estrogen Receptor Modulators (SERMs) that appear to prevent bone loss at the spine, hip, and total body. Like tamoxifen, is a selective estrogen receptor modulator (SERM), a drug that binds to the estrogen receptor and causes agonist activity in some tissues (eg. bone) and antagonist activity in other tissues (e.g. breast). Raloxifene has been shown to have beneficial effects on bone mass and bone turnover and can reduce the incidence of vertebral fractures by 30-50%. While side-effects are not common with raloxifene, those reported include hot flashes and deep vein thrombosis, the latter of which is also associated with estrogen therapy. Additional research studies on raloxifene will be ongoing for several more years. At the time of writing this article Raloxifene is not available in India but will be marketed very soon in India. It is important to realize that though the side-effects of Raloxifene are less compared to ERT it has hardly any action against the postmenopausal symptoms like hot flushes etc. It has got the same risk profile as estrogen as far as the risk of DVT goes.
Raloxifene (60 mg/day) reduced spine fracture risk by 50% in women with no fractures and by 30% in women with prevalent spine fractures; it also reduced the risk for ankle fractures (by 40%), but not hip or wrist fractures.
Calcitonin : Calcitonin is a naturally occurring non-sex hormone involved in calcium regulation and bone metabolism. In women who are at least 5 years beyond menopause, calcitonin slows bone loss, increases spinal bone density, and according to anecdotal reports, relieves the pain associated with bone fractures. Calcitonin reduces the risk of spinal fractures and may reduce hip fracture risk as well. Studies on fracture reduction are ongoing. Calcitonin is currently available as an injection (to be given subcutaneously) or nasal spray. While it does not affect other organs or systems in the body, injectable calcitonin may cause an allergic reaction and unpleasant side effects including flushing of the face and hands, urinary frequency, nausea, and skin rash. The only side effect reported with nasal calcitonin is a runny nose. Injectible calcitonin is available in India but nasal spray is not yet available. It is also used as a pain-relieving agent in acute fractures (100 to 300 IU per day). Calcitonin has a centrally mediated pain relieving action which is not yet fully understood. This pain relieving action is not only useful to relieve pain in osteoporotic fractures but also in pathological fractures due to skeletal metastasis. It is to be administered subcutaneously.
Bisphosphonates
These are the most studied molecules in the treatment of osteoporosis. These compounds have a potent antiresorptive effect and are especially useful in the first five years after menopause or in other high turnover osteoporosis.
Cyclical (every 14 days) etidronate (first generation bisphosphonate) has been used widely in the treatment of Paget’s disease.
However they have side effects like GI disturbances, immune function depression and mineralization defects. New third generation bisphosphonates like Alendronate and Pamidronate (second-generation bisphosphonate) have lesser side effects than the first generation bisphosphonates but have to be used on continuous basis. The dose of etidronate is 7mg/kg on cyclical basis (14 days every 3 months) in the treatment of osteoporosis. We now have Risidronate and Ibandronic Acid available in India. Ibandronic acid has an added advantage that it needs to be taken only once a month!
Vitamin K
The most neglected drug in the treatment of osteoporosis is Vitamin K. It is important for normal bone health because it mediates the gamma carboxylation of glutamic acid residues resulting in binding of calcium, helps in inhibition of calcium mineralization in urine, osteoclast homeostasis and synthesis of osteocalcin. Fortunately the daily requirements of vitamin K can be met with a diet full of green leafy vegetables.
Calcium
Maintaining positive calcium balance is the most important objective in treatment of osteoporosis. Everyone knows the requirements of calcium in various age groups (see table) but there is a lot of confusion about which salt of calcium to be prescribed.
Firstly only elemental calcium is available for absorption. Most of the ingested Calcium is absorbed from the intestines. Children absorb 75 % of ingested calcium but adults can only absorb 30 to 50 % of ingested dose and this ability further decreases as one starts aging. Calcium carbonate contains 40% of calcium in elemental form, citrate 24% and gluconate 9%. Calcium citrate however is more bioavailable than carbonate. Carbonate however is the cheapest salt available. Generic calcium supplements may not have calcium in bio-available form. The disintegration and dissolution of a tablet is critical for calcium absorption. Whether a tablet is good or bad can be determined by placing it in white vinegar solution for 30 minutes. A good tablet should totally dissolve in 30 minutes.
Timing is also crucial. Calcium taken several times a day is better than once a day because it is less likely to saturate the calcium absorption mechanism in the intestine this way. Remember that calcium also has a diurnal metabolism i.e. it is stored during the day and released at night. Achlorhydria (lack od acid in the stomach) impairs Calcium absorption and achlorhydria is very common in elderly and postmenopausal women. Calcium citrate does better than carbonate in this regard and therefore is the salt of choice in elderly. If 500mg of calcium is needed then prescribe it at night and greater than that should be equally divided but no single dose should be greater than 500mg. Calcium carbonate is best given with meals.
The commonest misconception is that calcium causes renal stones. Firstly the patients who develop renal stones form the stones because they can not keep the calcium in the urine in soluble form and not because of excessive calcium intake. Also, it has been proved that calcium in physiological doses never causes renal stones in normal individuals. Calcium citrate inhibits oxalate crystallization and should therefore be the preparation of choice for women with risk of forming renal stones. It is advisable to ask the patients to drink plenty of fluids while on calcium therapy. There are combinations of calcium with either alfa calcidol or even calcitriol which may not fulfil the requirement of patient’s need of calcium and at the same time prove very expensive.
Calcium phosphorous ratio
It has been mentioned in the literature that excessive phosphorous in diet retards the absorption of Calcium. Currently the issue is controversial and it is recommended that the dietary ratio of Calcium to phosphorous should be 2:1. Unfortunately in our country very few food packets divulge these ratios. In this scenario it is advisable to cut down on cola drinks, red meat and anything which is known to have excess phosphorous.
Vitamin D
Vitamin D is essential for absorption of calcium from the gut. Exposure to sunlight is important for the natural synthesis of Vitamin D. However in many of the polluted Indian cities the sunlight hardly reaches the skin!. Vitamin D deficiency is far more common in the affuluent classes these days due to life spent indoors and almost zero exposure to sunlight. The normal requirement is between 400 to 800 IU. Vitamin D is converted to alfacalcidol and then the active metabolite calcitriol in the body. Due to aging kidneys fail to produce enough quantity of enzyme Alfa hydroxylase which converts vitamin D into alfacalcidol. In elderly population therefore it may be prudent to give Vitamin D in the form of alfacalcidol. Patients who do not have ant functioning kidney end up having renal osteodystrophy and these patients require calcitriol to prevent osteoporosis.
Other Drugs
Teriparatide : Probably the best available drug today. It is the only drug which forms new bone. Unfortunately it has a few disadvantages. It is injected like insulin on a daily basis and the cost is staggering. Those who can afford to spend roughly 21000 Rs.per month for 18 months can go for it!
Guidelines to therapy : All women at menopause should be given a choice to start ERT after screening. Once on ERT they do not require BMD measurements till 65years. Those who are not willing to take ERT or those who have associated risk factors should undergo BMD testing and should be then given alternative therapy. Calcium and Vitamin D intake has to be assured. Counseling about lifestyle, diet, exercises and fall prevention should be included in the therapy as a routine.
The Basics Of Bmd Measurement
Measurements of BMD at any skeletal site have value in predicting fracture risk.
A variety of densitometers are in clinical use and provide reliable assessment of fracture risk. However, hip BMD is the best predictor of hip fractures, and it predicts fractures at other sites as well as other measurements. Thus, the recommendations made here are based on measurements of the hip. Because absolute values can vary with different densitometers, BMD is expressed as a relationship to two norms: the expected BMD for the patient’s age and sex (Z-score), or for “young normal” adults of the same sex (T-score).
The difference between the patient’s score and the norm is expressed as a standard deviation (SD) above or below the mean. (Usually, 1 SD equals a 10% to 12% difference in bone density.) T-scores decline in parallel with the steady drop in bone mass that occurs with aging (see Figure 3). This guide uses T-scores for clinical decision making.
In the above example, the BMD of a 57-year-old woman is expressed in comparison to young-normal average BMD (T-score) and age-matched average BMD (Z-score). Thus, this same woman has a Z-score of -1 and a T-score of -2.5.
who should be tested?
The decision to test for BMD should be based on an individual’s risk profile, and testing is never indicated unless the results could influence a treatment decision.
BMD testing should be performed on
All postmenopausal women under age 65 who have one or more additional risk factors for osteoporotic fracture (besides menopause)
All women aged 65 and older regardless of additional risk factors
Postmenopausal women who present with fractures (to confirm diagnosis and determine disease severity)
Women who are considering therapy for osteoporosis, if BMD testing would facilitate the decision
Women who have been on hormone replacement therapy for prolonged perio
