Osteoporosis is the most common metabolic bone disorder, affecting 200 million individuals worldwide. It is increasing in prevalence and remains largely underdiagnosed and undertreated. This is attributable in part to the fact that it is a clinically silent disease until it manifests in fracture. After this occurs, there can be significant pain, deformity, and increased morbidity and mortality.
The undertreatment of patients with osteoporosis is a serious issue. After patients are diagnosed with osteoporotic fractures, they may not receive appropriate medical treatment. Freedman et al19 showed that in 1162 women who had distal radial fractures, only 24% had either diagnostic evaluation or treatment of fracture, 2.8% had a bone density scan, and 22.9% were treated with at least one antiosteoporotic medication. Kiebzak et al35 showed that although women are treated inadequately for osteoporosis, men may be neglected even more. In a study involving 363 men and women with hip fractures, only 27% of men were receiving any treatment for osteoporosis, compared with 71% of women. However, adequate medical treatment seems to be improving. Gardner et al20 showed that in 75 patients from the years 1997, 1998, 1999, and 2000, 11%, 13%, 24%, and 29%, respectively, were given a prescription for medication targeting osteopenia, representing a significant increase in the rate of treatment.
Each year in the United States, there are 1.5 million osteoporotic fractures.57 Of these, 700,000 occur in the spine, 300,000 occur in the hip, and 200,000 occur in the wrist.
Patients who have one osteoporotic fracture are at increased risk for having another osteoporotic fracture develop. For example, the presence of one or more vertebral fractures results in a fivefold increased risk of having another vertebral fracture develop.44
The lifetime risk of fractures of the hip, wrist, and spine is 40%. The lifetime risk of hip fracture for a woman is 14%, and risk increases with age. At 80 years, 20% of women will have a hip fracture, and at 90 years, approximately 50% of women will have a hip fracture. Women who are older than 85 years are approximately eight times more likely than women 65–74 years to be admitted to the hospital for a hip fracture. In addition, there is increased morbidity and mortality for patients with osteoporosis, which will be discussed later. These overwhelming statistics warrant adequate physician and patient recognition.
We will provide an overview of osteoporosis, including its pathophysiology, risk factors, workup, clinical presentation, and adverse consequences. In addition, treatment approaches are reviewed, including medical treatment, involving calcium and vitamin D, the bisphosphonates, calcitonin, estrogen, selective estrogen receptor modulators (SERMs), parathyroid hormone, and nonmedical treatment, including vertebroplasty and kyphoplasty, hip protectors, posture training supports, and balance and exercise training programs. Novel interventions, such as the use of intravenous bisphosphonates and the minimally invasive procedures vertebroplasty and kyphoplasty, represent some of the most exciting areas to date, and recent data will be reviewed.
Homeostasis of bone, a living tissue,39 is maintained by the osteoclast, which is responsible for bone resorption, and the osteoblast, which is responsible for bone formation. Increased bone resorption or decreased bone formation may result in osteoporosis. Peak bone mass is reached at the age of 25–30 years in women. In men, there is a slow decline of bone mineral density (BMD). In women, there is accelerated loss of bone during the perimenopausal period, with slowing of the rate of loss several years after menopause. By the age of 60 years, women and men have equal rates of bone loss, with accelerated loss of total bone mass at the age of 80 years. As one ages, there are adverse effects on bone quality, including accelerated osteocyte death, increased bone turnover, thinned trabeculae, decreased cortical width, and increased cortical porosity. The strength of the bone is related to the bone mass, the distribution of the mass, and the quality of the bone.
Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to enhanced bone fragility, and increased fracture risk. The World Health Organization21 has defined osteoporosis on the basis of BMD measurements obtained on dual energy xray absorptiometry (DEXA) as a T-score of greater than 2.5 standard deviations below the mean for normals, who are young healthy individuals at their peak bone mass. A low BMD is associated with increased fracture risk.14 Low bone density may be secondary to failure to achieve optimal bone mass, bone loss caused by increased bone resorption, and inadequate replacement of lost bone as a result of decreased bone formation.
Prevention of Osteoporosis
The optimization of bone density during childhood and adolescence can help reduce the risk of having osteoporosis develop. In addition, a diet rich in calcium and vitamin D, a healthy lifestyle without smoking or excessive alcohol intake, and weightbearing exercise all may reduce the risk of osteoporosis. Appropriate BMD testing can aid the early diagnosis of osteopenia and osteoporosis. Regular menstrual cycles are essential in premenopausal women to maintain bone density.3 Prolonged periods of amenorrhea can result in bone loss.
Causes of Osteoporosis
Osteoporosis may be categorized into primary and secondary causes. Primary osteoporosis may be subdivided into Type I, postmenopausal osteoporosis, which is associated with menopause or estrogen deficiency, and Type II osteoporosis, age-related or senile osteoporosis, which affects men and women older than 70 years. Secondary causes include medications, endocrine disorders, chronic renal disease, hematopoietic disorders, immobilization, inflammatory arthropathy, nutrition and gastrointestinal (GI) disorders, and connective tissue disorders.
Female Athlete Triad
The female athlete triad is a complex triad that includes osteoporosis or premature bone loss, amenorrhea, and disordered eating. This triad commonly affects young women involved in sports in which physical appearance is paramount, such as figure skating and gymnastics. Disordered eating results in amenorrhea, leading to bone loss, which increases risk for fracture. The primary factor seems to be the caloric deficit, leading to the reproductive disorder.47 This, in turn, may predispose the athlete to premature osteoporosis and stress fracture.61
Work-up for osteoporosis includes laboratory studies including calcium, 25 hydroxy vitamin D levels, parathyroid levels, bone alkaline phosphatase, urinary calcium and creatinine, thyroid stimulating hormone, complete blood count, serum and urine protein electrophoresis, and liver function tests, to rule out underlying causes of osteoporosis.
Markers of bone formation and resorption include alkaline phosphatase and urinary Type I collagen-crosslinked N telopeptide (NTX), respectively. An elevated NTX level ( > 40 mmol/L BCE/mmol creatinine) can represent a high bone turnover state, and these markers can help determine the response to pharmacologic treatments.
Bone Mineral Density
Bone mineral density may be measured using DEXA, quantitative CT scanning, calcanometer, or other less commonly used modalities. However, DEXA is considered the gold standard because it is the most accurate modality used,65 has excellent precision, and measures central bone mass. Dual energy xray absorptiomety involves scanning the lumbar spine, the hip, and sometimes, the distal radius. Inaccurate results may be obtained if there is significant osteoarthritis in the spine or hip, if the patient is very tall or very short, if different machines are compared, and if there is improper positioning of the patient. Furthermore, men, African-Americans, and Latinos have higher BMD than Caucasians.46 In addition, Asians are known to have a slightly lower BMD secondary to their smaller size.59,60
Bone mineral density is known to be the most accurate predictor of fracture risk, and fracture risk is inversely related to BMD. T-scores and Z-scores represent densitometric values and represent the number of standard deviations above or below the mean for controls at their peak BMD, and age-matched controls, respectively. The World Health Organization1 has defined osteoporosis as a T-score of less than 2.5 standard deviations, and has defined osteopenia as a T-score of −1–−2.5 standard deviations. If a Z-score is less than −1.5 standard deviations, secondary causes of osteoporosis should be considered. For each standard deviation below peak bone mass, risk of fracture is increased twofold in the spine and by 2.5 times in the hip.40
Indications for obtaining BMD have been set forth by the National Osteoporosis Foundation, and include all white women 65 years or older not receiving antiosteoporotic therapy, postmenopausal women 50–65 years with a risk factor for osteoporosis,8 and individuals who have sustained a low-energy fracture.
Osteoporosis is a clinically silent disease until it manifests in the form of fracture. The most common sites of osteoporotic fracture are the vertebrae, followed by the hip and distal forearm.2 Diagnostic imaging, such as plain radiographs, bone scans, CT scanning, and MRI scanning, can aid the diagnosis of osteoporotic fractures. Two-thirds of all vertebral fractures are clinically silent, and only may be diagnosed using diagnostic imaging. Patients may present with complaints of loss of height, kyphotic posture without pain, or acute bony pain.
Osteoporosis Risk Factors
The National Osteoporosis Foundation has categorized risk factors for osteoporosis into nonmodifiable and potentially modifiable risk factors.27 Nonmodifiable risk factors include personal history of fracture as an adult, history of fracture in a first-degree relative, Caucasian race, advanced age, female gender, dementia, and poor health or frailty. Potentially modifiable risk factors include current cigarette smoking, low body weight (< 127 lb), estrogen deficiency, early menopause or bilateral ovariectomies, prolonged premenopausal amenorrhea, impaired vision despite correction, alcoholism, recurrent falls, inadequate physical activity, low life-long calcium intake, and poor health or frailty.
Adverse Sequelae of Osteoporosis
Osteoporosis can result in permanent skeletal changes if untreated, resulting in fracture. Vertebral fractures can lead to increased thoracic kyphosis and decreased size of the thoracic and abdominal cavities, and result in pain, postural changes, decreased tolerance for oral intake, abdominal protrusion, and iliocostal friction. Pain may result from vertebral fractures and the resulting kyphosis. Pain and these physical changes may lead to depression,13,23 social isolation, and low self-esteem,24 with overall diminished quality of life.53
Morbidity and Mortality
Furthermore, osteoporotic fractures, particularly vertebral fractures and hip fractures, significantly increase morbidity and mortality. Kado et al32 showed that women with one vertebral fracture had a 1.23x increased age-adjusted mortality rate, and that women with five or more vertebral fractures had a 2.3x increased age-adjusted mortality rate. Mortality increased with greater number of vertebral fractures, from 19 per 1000 woman-years in patients with no fractures to 44 per 1000 woman-years in those with five or more fractures (p for trend, < 0.001). Vertebral fractures were related to increased risk of subsequent cancer and pulmonary death. Hip fractures also significantly increase morbidity and mortality, with only 50% of elderly patients admitted to the hospital for hip fractures able to return home or live independently after injury.32 Twenty-five percent of patients who have had hip fractures die within the year because of complications, 50% need a cane or walker after fracture, and only 25% of patients make a full recovery.32
Pharmacologic treatment of patients with osteoporosis includes calcium and Vitamin D, bisphosphonates, calcitonin, estrogen, and selective estrogen receptor modulators. New medications in development show promise in the treatment of osteoporosis. Treatment of pain is essential to promote increased mobility.
Calcium and Vitamin D
A daily requirement of 1200–1500 mg of calcium is recommended. Calcium may be obtained in the diet from such foods as dairy products. Supplemental calcium is available in the form of calcium citrate and calcium carbonate. Calcium citrate tends to be better absorbed than calcium carbonate because it dissolves at all pH levels. Calcium carbonate requires an acid environment and is compromised by H2 blockers. Oral forms of calcium carbonate, such as in antacids or chews, are good sources of calcium for patients who take antacids. Vitamin D should be taken with calcium, and a daily dose of 400–800 IU is recommended, with the higher dose recommended for elderly patients with little sun exposure. In addition, patients who have vitamin D deficiency should be treated with supplemental vitamin D, usually 50,000 IU as needed. The administration of calcium and vitamin D has been shown to prevent hip fractures and nonvertebral fractures in elderly women. Chapuy et al11 observed 1765 elderly women living in nursing homes or apartment houses for the elderly who received 1200 mg of elemental calcium and 800 IU of vitamin D3 (cholecalciferol) daily for 18 months. They reported that there were 43% fewer hip fractures and 32% fewer nonvertebral fractures in the group receiving calcium and cholecalciferol compared with the group receiving placebo. In a followup study, Chapuy et al10 showed that the administration of 1200 mg of elemental calcium and 800 IU cholecalciferol daily for 36 months in 3270 elderly women resulted in a continued preventive effect of calcium and cholecalciferol supplementation on the risk of hip fracture. Using an intention to treat analysis, 23% fewer subjects had one hip fracture and 17.2% fewer subjects had one or more nonvertebral fractures. There was a decreased probability of hip fractures (p < 0.02) and all nonvertebral fractures (p < 0.01), with an odds ratio of 0.73 for hip fractures and 0.72 for all nonvertebral fractures.
Bisphosphonates are the most potent class of drug in the prevention and treatment of osteoporosis. This class of drugs are pyrophosphate analogs, which strongly bind to the hydroxyapatite of bone, inhibiting osteoclast activity. Alendronate and risedronate are the two main oral bisphosphonates used and decrease the fracture rate for the spine and hip. In addition, the intravenous bisphosphonates pamidronate and zolendronate have been used off-label for the treatment of osteoporosis. Adverse effects for the oral bisphosphonates include GI complications such as gastritis or esophagitis, abdominal pain, nausea, vomiting, diarrhea, and constipation, particularly in a prone (hospitalized) patient. To minimize GI inflammation and ulcers, patients must remain upright for at least 30 minutes after taking the medication. In patients with a questionable history of gastroesophageal reflux disease, incremental dosage increases are advisable. Tolerance generally is improved with a once-weekly dosing regimen versus daily dosing. Adverse effects for patients who are given the intravenous bisphosphonates include fevers and a flulike syndrome. The administration of concurrent acetaminophen and antihistamine helps to minimize the risk of these transient complications.
Alendronate has been proven effective in postmenopausal osteoporosis in increasing BMD and decreasing the risk of vertebral and nonvertebral (hip) fracture. Black et al4 observed 2027 women with preexisting vertebral fractures and reported that 5 mg alendronate administered daily for 24 months, and then increased to 10 mg, resulted in fewer radiographic vertebral fractures in the treatment group versus the placebo group. There was an average increase in the lumbar spine BMD of approximately 5% after 1 year, and then 1.5% per year for the next 2 years. At the end of 3 years, there was an increase in BMD of approximately 6% in the femoral neck and approximately 7% in the trochanter. Black et al6 did the Fracture Intervention Trial (FIT), in which they observed 3658 women with osteoporosis with either existing vertebral fracture or osteoporosis at the femoral neck, but without vertebral fracture, and were treated with alendronate for 3–4 years. They reported that there was decreased risk of fracture in the treated women, with a 0.47 relative risk of fracture in the hip, 0.52 relative risk of radiographic vertebral fracture, 0.55 relative risk of clinical vertebral fracture, and 0.70 relative risk of all clinical fractures. Alendronate has shown significant efficacy for men and individuals on steroids. One weekly dose is as clinically effective as daily dosage but with lower dyspepsia.
Risedronate also has been shown to be effective in increasing BMD and in reducing fracture risk. Fogelman et al18 showed that a 5-mg oral daily dose of risedronate resulted in BMD increases after only 6 months of therapy, and that at 24 months, lumbar spine BMD increased from baseline by 4%, with increases of 1.3% and 2.7% seen in the femoral neck and femoral trochanter, respectively. Harris et al26 did a triple-blind, three-arm placebo controlled study in 2458 postmenopausal women, and reported that in patients receiving a 5-mg oral daily dose of risedronate, BMD increased in the femoral neck, femoral trochanter, and lumbar spine at 3 years by 3–4%. They also reported decreased risk of new vertebral and nonvertebral fractures.
Parenteral pamidronate also has been used off-label in the treatment of postmenopausal women with osteoporosis who are intolerant to oral bisphosphonates. Peretz et al54 showed that 36 postmenopausal women with osteoporosis who received five courses of cyclical intravenous pamidronate had reduced bone turnover. Guttmann and Van Linthoudt25 also showed that 13 patients who received 30 mg of pamidronate intravenously for 3 months had an increased BMD of 6.2% in the lumbar spine and 4.7% in the hip.
Parenteral zoledronate, also used off-label, administered at intervals of 1 year, produced comparable effects on bone turnover and BMD to those seen with oral dosing with bisphosphonates, and provides protection for the skeleton. Reid et al56 did a randomized, double-blind, placebo-controlled trial involving annual doses of zoledronate and documented increases in the treatment group for the spine that were 4.3–5.1% greater than those in the placebo group, with suppressed biochemical markers of bone formation. Fracture data for parenteral pamidronate and zoledronate have not been reported in the literature.
Nasal calcitonin is helpful in the treatment of bony pain secondary to fracture, and also works to increase BMD and decrease vertebral fracture risk. Typically, analgesia for bone pain is achieved as early as the first to second week of use. The mechanism of activity is not well-understood, although the endogenous opiate system may play a role in mediating the analgesic effects.22 Chesnut et al12 did a 5-year, double-blind, randomized, placebo-controlled study in 1255 women with established osteoporosis, and showed that the 200 IU dose reduces the risk of new vertebral fractures by 33% compared with placebo. There were gains of 1–1.5% in the lumbar spine BMD in patients receiving 100, 200, and 400 IU of calcitonin daily. However, calcitonin does not provide any fracture protection to the hip.49,62
Estrogen and Selective Estrogen Receptor Modulators
Estrogen used for the alleviation of symptoms after menopause may increase bone density, but is not used as a primary agent in the treatment of osteoporosis. Although estrogen has been shown to decrease the incidence of hip and spine fractures by 35%, it has many potential complications and therefore is not recommended for use in osteoporosis. Recently, the Women’s Health Initiative Writing Group58 reported that per 10,000 person years, there were five fewer hip fractures, but there were seven more coronary heart disease events, eight more strokes, eight more pulmonary embolisms, and eight more invasive breast cancers in patients receiving conjugated equine estrogens plus progestin. They concluded that the overall health risks from estrogen exceeded the benefits from use.
Selective estrogen receptor modulators such as raloxifene may increase BMD, but also are not as effective agents as bisphosphonates in the treatment of osteoporosis. Maricic et al48 reported that in patients treated with 60 mg daily doses of raloxifene, there were 68%, 46%, and 41% decreased risks of new clinical vertebral fractures at 1, 2, and 3 years, respectively, but there was no hip fracture protection. However, the selective estrogen receptor modulators have been associated with venous thromboembolism and hot flashes.50
Parathyroid hormone (PTH) is a new anabolic agent approved by the Food and Drug Administration (November 2002) that promises to treat osteoporosis efficaciously. Parathyroid hormone works by increasing bone resorption and bone formation, increasing BMD, and enhancing bone architecture and integrity.7 Studies have shown that PTH increases the connectivity density of bone,15 thickens trabeculae,55 increases cortical thickness, and inhibits osteocyte apoptosis,31 thereby reducing risk of fracture. Neer et al52 did a double-blind, controlled trial involving 1637 postmenopausal women with vertebral fractures and reported that a 20-μg subcutaneous dose of teriparatide, recombinant human PTH (1–34), resulted in 10% and 2.8% increases in lumbar and hip spine BMDs, respectively. In addition, risk of new vertebral fractures was decreased by 65%, and risk of nonvertebral fractures was decreased by 54% but only after 10 months compared with a less than 6-month administration for the bisphosphonates. Body et al7 showed that a once-daily 40-μg subcutaneous dose of teriparatide, recombinant human PTH (1–34), compared with a 10-mg daily dose of alendronate, resulted in increased lumbar spine BMD (12.2% versus 5.6%, respectively). Overall, recombinant human PTH (1–34) increased femoral neck BMD, total body bone mineral, and decreased nonvertebral fractures. In comparison to bisphosphonates, PTH takes 3–6 months longer to provide fracture protection. More recent studies have highlighted the fact that there remains no clearcut treatment logarithm involving PTH. For example, it is unclear whether PTH should be given alone first, in combination with a bisphosphonate, or if a bisphosphonate should be administered alone first. Recent authors have reported that combination therapy of PTH and a bisphosphonate did not result in synergistic effects, but rather resulted in diminished BMD gains compared with PTH alone. Black et al5 found that female postmenopausal patients who received 100 μg (range, 1–84) PTH alone had increases in the trabecular bone at the spine that were twice that of patients who received 10 mg alendronate daily or a combination of 10 mg alendronate daily with 100 μg of PTH (range, 1–84). Finkelstein et al17 did a study in men, administering alendronate 10 mg daily, parathyroid hormone 40 μg daily, or both, and found that parathyroid hormone resulted in significant increases in BMD of the spine and femoral neck compared with the alendronate or combination groups. Patients in the combination group received alendronate therapy for 30 months, with PTH therapy beginning at 6 months. Patients who received combination therapy had greater increases in BMD of the lumbar spine compared with the alendronate group. These studies show that PTH seems to produce more favorable results than combination therapy of PTH and alendronate, which in turn produces more favorable results than alendronate alone. This may be attributed to diminution of PTH-induced bone formation by alendronate. At this time only bone density comparisons are available. There are no data regarding fracture protection.
Nonpharmacologic treatment of osteoporosis includes vertebroplasty and kyphoplasty, hip protectors, posture training supports, and balance and exercise training programs. Vertebroplasty and kyphoplasty are two new minimally invasive procedures used in the treatment of vertebral compression fractures. Initially used for pathologic fractures, these procedures now represent important therapeutic interventions for patients with osteoporotic vertebral compression fractures. Both involve the infiltration of PMMA into fractured vertebral bodies; the difference is that kyphoplasty attempts to restore vertebral body height with the use of a balloon inserted into the vertebral body, which compacts the cancellous bone and reexpands the fracture, whereas vertebroplasty bypasses this step. Kyphoplasty can partially restore vertebral body alignment and height.38 Both procedures have been shown to be successful in pain reduction, and kyphoplasty has been shown to result in significant improvements observed in SF-36 scores and vertebral body height.41 Lieberman et al41 reported the results of 70 consecutive kyphoplasty procedures in 30 patients with osteoporotic vertebral compression fractures. They reported that in 70% of the vertebral bodies, there was 47% restoration of lost height and significant improvement in Short-Form-36 scores for bodily pain and for physical function. Bodily pain scores improved from 11.6–58.7 (p = 0.0001), and physical function scores improved from 11.7–47.4 (p = 0.002). Dudeney et al16 reported the results of 55 kyphoplasty procedures in 18 patients with osteolytic vertebral compression fractures resulting from multiple myeloma and showed that an average of 34% of height was restored to the fractured vertebral bodies, and that improvements in bodily pain scores occurred from 23.2–55.4 (p = 0.0008), physical function scores from 21.3–50.6 (p = 0.001), vitality scores from 31.3–47.5 (p = 0.01), and social function scores from 40.6–64.8 (p = 0.014). Theodorou et al67 also reported their experiences involving kyphoplasty in 15 patients with painful osteoporotic vertebral compression fractures and reported that on average, kyphoplasty improved kyphosis by 62.4%, and that all patients experienced dramatic pain relief. At this time vertebral restoration seems to be more beneficial in patients with continued loss of vertebral height (> 40%), the presence of moderate pain (visual analog scale > 4/10), or both, after 1 month of conservative care.
Hip protectors, usually made of polypropylene, are a simple and efficacious device that can reduce the risk of hip fracture significantly. Some studies to date have shown that if used, these orthoses are successful in reducing hip fractures. Kannus et al33 did the largest, randomized controlled trial to date involving 1409 women and 392 men at high risk of falls. They reported that the rates of hip fracture were decreased in the hip protector group compared with the control group. They concluded that 41 persons needed to use hip protectors for 1 year, or eight persons for 5 years, to prevent one hip fracture. The major drawback to their use is compliance. Hip protector compliance rate has ranged in the literature from 35.9%28 to 48%.33 These orthoses may be difficult to manipulate, because most are in the form of undergarments that are difficult to wear and remove, particularly for elderly patients with poor balance and manual dexterity. In addition, patients with incontinence may have increased difficulties with the hip protectors. However, in addition to preventing hip fractures, hip protectors have been shown to improve self-confidence. Cameron et al9 reported that elderly women who used hip protectors had improved self-efficacy, defined as the belief in their own ability to avoid falling.
Posture Training Supports
Posture training supports have been shown to reduce symptoms associated with kyphosis and vertebral compression fractures. These devices are lightweight orthoses worn backpack-style, which come with 1 ¾ lb weights. They are used in patients with symptomatic thoracic kyphosis, particularly secondary to vertebral compression fractures. Kaplan et al34 reported that the posture training support had better compliance than a conventional thoracolumbar support. Furthermore, there was an increase in back extensor strength in patients compliant with the posture training support and postural exercise program. Back extensor strength, in turn, has been shown to reduce thoracic kyphosis29,63 and reduce vertebral fracture in estrogen-deficient women.64 However, there have been no prospective, randomized, controlled trials to date involving the posture training support.
Balance and Exercise Training
Balance training programs, especially tai chi chuan, have been shown to improve balance and have been associated with a 47.5% reduction in risk of falls.68 Tai chi chuan seems to improve balance when patients are challenged in disturbed visual and somatosensory conditions.43,69
Exercise training can increase BMD, although an actual decrease in fracture rate is not documented.42 Snow et al66 reported that postmenopausal women who wore weighted vests and participated in jumping exercises three times per week for 32 weeks annually during 5 years had a 1.54% increased BMD of the femoral neck. Kujala et al37 showed in a prospective cohort study involving 3263 men that there was an inverse relationship between baseline physical activity and future hip fracture risk among men, with a 0.38 hazard ratio of osteoporotic hip fracture in men participating in vigorous physical activity compared with sedentary men. However, Iwamoto et al30 stated that in postmenopausal women with osteoporosis, continued exercise training is necessary to maintain bone mass gained with exercise training.
Osteoporosis is an increasingly prevalent condition that can result in significant functional limitations and increased morbidity and mortality. Although appropriate treatment of osteoporosis has been lacking, this trend seems to be improving, with growing numbers of patients receiving appropriate treatment. Early diagnosis, appropriate medical treatment with medications such as calcium and vitamin D, the bisphosphonates, and PTH, the appropriate balance and exercise training programs, and the minimally invasive procedures vertebroplasty and kyphoplasty comprise some of the key components of a multidisciplinary approach to treating osteoporosis. Medical treatments such as calcium and vitamin D and the oral bisphosphonates are principal components of a medical approach. Intravenous bisphosphonates may be used in patients unable to tolerate oral bisphosphonate, although this treatment is off-label and available only at limited centers. Intravenous bisphosphonates have been shown to have similar effects on BMD as oral bisphosphonates, although fracture data have not been reported to date.
The appropriate starting point for treatment is controversial in the medical management of osteoporosis. In postmenopausal women it is hard to prove that there is fracture protection for the individuals with osteopenia because of the difficulty in identifying poor quality bone. This difficulty in identification needs to be resolved to identify the individuals most in need of treatment. Individuals with osteopenia have a loss of trabecular connectivity, and with the exception of PTH, none of the antiosteoporotic agents lead to reconnectivity. Therefore, earlier treatment is still appealing without fracture prevention data. In addition, how long to medically treat osteoporosis remains unclear. Prolonged bisphosphonate treatment, greater than 5 years, might lead to accumulation of microfractures from damage and the inability to remodel those sites. These seems to be no diminution of fracture prevention after cessation of bisphosphonate treatment, but the accumulation of bisphosphonates may lead to prolonged protection even after stopping the agents. Currently, bisphosphonate treatment usually ends after more than 5 years with plateauing of bone mass measurements and low bone turnover markers. Some physicians would not restart bisphosphonate treatment until the NTX begins to rise, whereas others advocate a 1–2 year rest period. Finally, there are some problems with the use of PTH. Hip fracture protection with PTH does not occur before 9–12 months whereas bisphosphonates prevent fractures after 6 months of treatment. However, PTH produces more bone (8% versus 2%). Clearly, there is a quality of bone issue. Combination PTH and bisphosphonates produce less bone than PTH alone and several authors have suggested giving PTH alone. There is no fracture prevention data comparing the two therapies directly or in combination. Currently, the difference in bone quality between these therapies is unknown. Complicating matters, bisphosphonates do not seem to delay fracture healing but do lead to prolonged presence of the callus and slow remodeling.36 This study was done in animals that readily heal.36 There is neither direct analysis of patient fracture healing nor animal studies in compromised fracture healing models. Therefore the role of bisphosphonates in difficult fracture healing situations is not clearly defined. However, bisphosphonates have been shown to prevent disuse osteoporosis in the ipsilateral limb during fracture repair.45 Parathyroid hormone has been shown to enhance fracture repair in numerous animal models.51 Its benefit in humans is unknown. There is no information on the effect of PTH on ipsilateral limb disuse osteoporosis. Therefore, with a newly recognized fracture and osteoporosis, it is not clear which antiosteoporotic drug should be chosen, and the timing and sequence of its administration.
The long-term biomechanical effects of vertebroplasty and kyphoplasty are unknown, and the relative superiority of one procedure over the other is controversial. Despite these controversies, these components are some of the most exciting current treatments for osteoporosis. With the many options, a comprehensive, meticulous interdisciplinary approach can help to optimize the treatment, and in turn, improve functional outcomes and quality of life for patients with osteoporosis. The scope of the problem of osteoporosis necessitates close attention to the appropriate treatment of patients with osteoporosis either by the orthopaedist, physiatrist, or other physician.
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