Osteoporosis

Osteoporosis is a condition associated with an increased risk of bone fracture.  The increased risk is related to a decrease in the amount of calcium in bones causing a weakening of bone structure.  With decreased bone quality, individuals are at increased risk of spontaneous fractures as well as those associated with falls.  A primary location for fracture is the lumbar and thoracic spine.  Other skeletal structures at risk include the hips, pelvis, and wrists.

Osteoporosis is most common in Caucasian postmenopausal women.  To a lesser degree, Asian, Hispanic, and African-American women are at risk of fractures.  Men over 75 years of age account for about 20% of osteoporosis cases.  About 10 million Americans have osteoporosis.  Osteopenia is a condition of decreased bone mineral density but of the degree to be of significant risk of immediate fracture.  An additional 18 million Americans are osteopenic .

Osteoporosis is a serious medical condition.  In the year following a hip fracture, up to 20% of patients die.  Rehabilitation care is required for another 20% and 50% of individuals never fully recover.

What are the Symptoms of Osteoporosis?

Bone is living tissue that is constructed like a building.  Buildings have an internal framework,  girders, that are surrounded by cement to form rooms.  The equivalent in bone for girders is collagen and for cement is calcium and phosphorus.  Bone is constantly remodeled by cells that excavate (osteoclasts) and refurbish (osteoblasts).  This process supplies a constant source of calcium that supports essential bodily function as heart beats and muscle contractions.  When we are younger, the balance is in favor of osteoblasts that make bone.  As we age, the balance shifts to the excavating cells, osteoclasts that hasten bone loss.  As calcium is lost from bone, the architecture is altered with cross struts supporting weight being lost.  The result is weakened bone with increased fracture risk.

A postmenopausal, older, thin, smoking, Caucasian woman illustrates the primary risk factors for osteoporosis.  Certain medicines, like corticosteroids, and medical conditions, hyperparathyroidism, increase the risk of secondary osteoporosis.  Other causes of bone loss or bone expansion resulting in fracture include cancer (multiple myeloma), bone death (sickle cell anemia) or infection (osteomyelitis).

The majority of osteoporotic individuals are asymptomatic.  Bone loss without fracture is a painless process.  Loss of bone can result in microfractures that do not result in change in the shape of vertebrae.  An ache can be associated with this change in bone structure.

Osteoporotic fractures cause spinal pain localized in the middle of the back over the corresponding vertebra.  Acute fractures create sudden onset of severe pain.  In this circumstance, height loss does occur.

How is Osteoporosis Diagnosed?

Osteoporosis is diagnosed in individuals who experience nontraumatic fractures of the spine, hip, or wrist.  These fractures can occur in the setting of a fall from low heights.  Some individuals fracture their hip and then fall.  In the absence of a fracture, bone mineral density (BMD) can be used to diagnose osteoporosis.  The World Health Organization (WHO) defines osteoporosis as a T score < -2.5 standard deviations below the mean value of peak bone mass.  Osteopenia is a BMD score between -1 and -2.5.

A tool to predict the 10 year risk of developing hip or spine fractures is the Fracture Risk Assessment (FRAX) tool developed by the WHO.  The tool is available on the web at www.shef.ac.uk/FRAX.  The tool takes into account eleven clinical risk factors and hip BMD, if available, to give the risk of developing fractures.  A fracture risk of any bone of 20% or 3% for the hip is an indication for treatment of osteoporosis. (see DXA section)

Men and Osteoporosis

Osteoporosis is less common in men than women.  Men have more bone than women to start.  Bone loss starts later in life.  Bone loss does occur in men as testosterone levels decrease.  The ability to absorb calcium is decreased with age.  The risk for fractures also increases with the tendency to fall more often.  In men, hormone ablation therapy for prostate cancer can result in an increased risk.  By age 75, 25% of men are osteoporotic .

How is Osteoporosis Treated?

Prevention

The best treatment for osteoporosis remains prevention.  In the elderly, falls are a frequent cause of fractures.  A home can be filled with unsuspected hazards.  Slip rugs can slip and should be removed.  Staircases should be well-lighted.  Nonslip surfaces should be on the stairs and in bathtubs and showers.  Clutter should be removed.  Innumerable patients have described tripping over some object on the floor that they overlooked.  Pets need to be well-trained.  A leash can quickly become a tourniquet around the legs and down you go.  We love our pets, but they should not put their companions at risk.

Weight-bearing exercising, like walking, is essential to increasing or maintaining bone mineral density at any age.  Also, impact or resistance exercise, such as lifting weights, is positive for bone health.  These efforts will blunt bone loss but will not fully prevent it.

Calcium and Vitamin D

Calcium and vitamin D are essential to maintain bone health.  Calcium is an essential building block of bone.  Vitamin D is required for adequate absorption of calcium from the gastrointestinal tract.  Debate has surfaced regarding the appropriate daily intake of calcium.  Current recommendations suggest 600 mg of calcium with any remainder from dietary sources including dairy products, like milk or yogurt, and vegetables, like broccoli.  A variety of calcium supplements are available.  Calcium citrate is more easily absorbed.  Calcium carbonate is another form of calcium supplement.  The dose of vitamin D varies depending on the level in the bloodstream.  Vitamin D is made in our skin when exposed to the sun.  The difficulty is that northern latitudes do not have strong enough sun exposure to produce vitamin D year round.  In most individuals 1,000 IU (International Units) are adequate.  With those with severe deficiencies, weekly doses of 50,000 IU are given until normal levels are achieved.  Vitamin D can be quantified with blood tests.  Calcium and vitamin D are prerequisite therapies for the other therapies administered for osteoporosis.  The risk of toxicities with other agents are increased in the absence of these supplements.

Vinegar test

A vinegar test is a good means to determine if you calcium supplement is absorbable in the gastrointestinal tract.  Place your calcium pill in about a quarter cup of vinegar and swirl it around.  If in 30 minutes the pill has not dissolved, throw the supplement out and obtain a brand-name product.  If it does not dissolve in the vinegar, it will not dissolve in your stomach and will go all the way through without any absorption.

Hormone Replacement Therapy

Estrogen deficiency after menopause leads to bone loss.  The greatest rate of bone loss occurs in the first years after ovarian failure.  Estrogen replacement therapy or ERT has been used in postmenopausal women.  Replacement estrogen can maintain bone mineral density but cannot increase density in women who are already osteoporotic.  In addition, the Women’s Health Initiative, a large study of estrogen and progesterone replacement therapy reported an increase in cardiovascular disease and breast cancer in women on ERT.  Some women have severe estrogen deficiency symptoms including  hot flashes continue to take small amounts of estrogen which may have some effect on BMD.  The role of ERT remains an individual choice between a patient and their physician.

Raloxifene (Evista) is a selective estrogen receptor modulator with estrogen-like effects on bone resorption but without stimulating the lining of the uterus or breast tissue. The drug is administered as 60mg orally once a day.  Studies have demonstrated increased BMD in the spine but less in the hips.  Side effects from the medicine include blood clots, leg cramps, and hot flashes.

Calcitonin

Calcitonin (Miacalcin, Fortical) is a natural hormone that reduces bone breakdown in the human body.  The hormone is produced by the C cells in the thyroid gland.  The hormone is effective in decreasing the risk of fracture in the spine, but not as much in the hip.   Women five years post-menopausal who are unable to take bisphosphonates are candidates for this drug.  Men with normal testosterone levels are responsive to this agent. Calcitonin harvested from salmon is used as a nasal spray as a therapeutic agent for mild osteoporosis.  The recommended dose of calcitonin salmon nasal spray is 1 spray (200 units) per day alternating nostrils daily.  Side effects include nasal irritation and a small, increased risk of malignancy 4% versus 2% in normal populations.

Bisphosphonates

Bisphosphonates are the most commonly prescribed therapy for osteoporosis.  The concept behind these medicines was the interaction between detergents and hard water.  Bisphosphonates are similar  in structure to a component of bone.  Osteoclasts are the cells that break down bone during the remodeling process.  Bisphosphonates attach to the active sites on osteoclasts and prevents their activation.  By decreasing bone resorption, bone mineral density is increased by allowing a preference to bone forming cells, osteoblasts.  The effect on density is rapid within months.

Alendronate (Fosamax) is a bisphosphonate, 70 mg, taken orally on a weekly basis.  Alendronate has beneficial effects on bone mineral density in the spine and hip.  The effect on bone is prolonged.  Bone mineral density may increase by 5% to 10% over 2 to 4 years and reduce fracture risk by 30% to 50%. The optimal duration of therapy has not been determined.  Currently, bisphosphonate therapy is discontinued after 5 years.  The toxicities of oral bisphosphonates are greatest on the gastrointestinal tract with esophageal irritation.  They also have poor intestinal absorption.  The drug is taken in the morning after an overnight fast, with a large glass of water.  Remaining upright for 30 minutes is necessary to decrease the risk of to the esophagus. With movement of calcium into bones, muscles may become calcium deficient resulting in persistent cramping.  Bone and joint pain may also occur.

Risedronate (Actonel) is a bisphosphonate taken weekly at 35 mg or 150 mg once a month.  The drug increases bone mineral density in hips and spine.  Toxicities are similar to those of alendronate.

Ibandronate (Boniva) is administered orally or intravenously.  The oral form is given monthly in a 150 mg dose given the same day of the month.  The intravenous form is given by vein, 3 mg/3ml every 3 months.  The benefits on spine and hip are similar to other bisphosphonates as are the toxicities.

Zolendronic Acid (Reclast) is an intravenous form of bisphosphonate administered once a year.  Zolendronic acid reduces hip and spinal fractures and increases bone mineral density.  Infusions may be given for 3 years.  Infusions, given over 15 minutes or longer, are usually well tolerated with about 20% having 3 days of muscle or bone pain.  A much smaller group of patients may develop a severe bone pain syndrome that can last for months.

Another potential toxicity associated with all bisphosphonates is osteonecrosis of the jaw.  Osteonecrosis is an area of bone where cells have died.  The result is an area of bone that will disintegrate.  The risk for jaw osteonecrosis increases if dental repairs are conducted after bisphosphonate therapy is established.  Risk is increased the longer an individual takes bisphosphonates.  A recommendation is given to have dental work completed before initiating bisphosphonate therapy.  The risk of jaw necrosis is small in most individuals taking bisphosphonates.  Intravenous forms of bisphosphonates are more closely associated with this toxicity.

Another infrequent but significant toxicity which increases with prolonged therapy is atypical fractures of the femur.   The area of fracture is lower along the femur than the usual location in the neck of the femur.  The risk for fracture is low for the first 5 years of treatment and increase progressively with long-term exposure

Human Parathyroid Hormone

Parathyroid hormone is a naturally occurring protein associated with maintaining blood levels of calcium.  The source of calcium is bone.  When present in persistent levels, bone loss occurs.  When bone is exposed to small amounts, a contrary effect occurs on osteoblasts, causing a building of bone.

Teriparatide (Forteo) is an injectable form of parathyroid hormone. A daily injection into the abdomen or thigh of 20 mcg for 2 years is associated with significant improved bone density in the spine and the hip.  The drug is limited to a 2 year administration because longer duration of therapy is associated with the development of cancer in rats.  This form of therapy is indicated for those individuals with previous fractures or inability to tolerate bisphosphonates.  Toxicities associated with this injectable therapy include dizziness and nausea.

Anti-Rank Ligand (Rankl) Antibody

Rank ligand (RANKL) is a protein signal to osteoclasts to become active.  The result is a loss of bone mineral density.  Antibodies that block RANKL prevent the activation of osteoclasts thereby increasing bone mineral density.  Denosumab (Prolia) is a RANKL fully human antibody that binds to the protein.  Denusomab is administered as a 60mg/ml subcutaneous injection once every 6 months.  The beneficial effects can be detected within hours of the injection.  The beneficial effects are dissipated by 6 months.  Injections need to be repeated to have a sustained benefit. The full duration of Prolia therapy remains to be determined.  Potential toxicities are similar to those of bisphosphonates including bone pain, osteonecrosis of the jaw and atypical fractures of the femur.  An additional risk is that of cellulitis or other infections in individuals who are taking immunosuppressive agents like anti TNF antibody therapy.

Acute Fracture Therapy

Individuals who sustain vertebral body fractures are likely to lose height.  Instead of a rectangle, the vertebral body resembles a triangle. A curvature of the spine may occur if more than 1 neighboring vertebral body is damaged.  In addition, like any other fracture, pain is significant potentially limiting function.

In the setting of an acute fracture less than 6 to 8 weeks in duration, kyphoplasty may be able to restore some of the lost height making the vertebral body more like a trapezoid.  The procedure is attempted before the fracture has fully healed.  An inflatable balloon is passed into the flattened vertebral body and is expanded to restore height.  The balloon is removed and is filled with bone cement under low pressure.  The benefit of low pressure installation is the decreased risk of extrusion of the cement into the spinal canal.  Risk remains that the presence of bone cement will result in more fractures.   Medical therapy for osteoporosis is needed to improve bone mineral density.

Vertebroplasty is another spinal procedure that has fallen out of favor.  This technique was used in individuals with spinal curvatures secondary with healed fractures and spinal pain.  Bone cement was forced with high pressure into collapsed vertebral bodies.  The added cement was placed to stabilize the area with the expectation of decreased spine pain.  The increased risk is the development of new fractures and spread of cement into the spinal canal because of the need for high pressure.  A spine surgery is usually needed to remove the cement from the canal if spinal nerves are damaged.

CONDITIONS OF THE GI TRACT