Osteoporosis Xử trí

If a fracture is present upon screening, physical exams, laboratory tests, and radiologic tests should also be conducted to exclude underlying diseases that mimic, aggravate, or cause osteoporosis eg secondary osteoporosis (metabolic or endocrine causes, GI or nutritional conditions, collagen metabolism disorders, medications, AIDS or HIV, immobilization, organ transplantation, myeloma, and some malignancies).

Fracture Risk Categories

• Low risk: BMD T-score at both hip and spine >-1.0, and 10-year hip fracture risk <3%, and 10-year risk of major osteoporotic fractures <20%, with no prior hip or spine fractures
• Moderate risk: BMD T-score at both hip and spine >-2.5, or 10-year hip fracture risk <3%, or 10-year risk of major osteoporotic fractures <20%, with no prior hip or spine fractures
• High risk: BMD T-score at hip or spine of ≤-2.5, or 10-year hip fracture risk ≥3%, or 10-year risk of major osteoporotic fractures ≥20%, with a prior hip or spine fracture
• Very high risk: BMD T-score at hip or spine ≤-2.5 with multiple spine fractures, or 10-year hip fracture risk >4.5%, or 10-year risk of major osteoporotic fractures >30% (may also include patients with a fracture within the last 12 months, fractures while on osteoporosis therapy, fractures on long-term glucocorticoid therapy, multiple fractures, T-score <3.0, high risk for falls, or a history of injurious falls)

Bisphosphonates

Bisphosphonates are the first line of treatment for osteoporotic patients to reduce the risk of fracture and patients receiving glucocorticoids with osteoporotic fractures or established osteoporosis. These can be considered for prevention of bone loss in postmenopausal women with a T-score of <-1 and other risk factors for fracture who do not fulfill criteria for osteoporosis treatment. Bisphosphonates may reduce the risk of subsequent fractures in patients with prior or prevalent fragility fractures. These inhibit osteoclast activity and potent inhibitors of bone resorption and have no effect on menopausal symptoms. Evaluate the efficacy of treatment after 3 years on intravenous (IV) therapy and 5 years on oral therapy. If ineffective (ie declining bone mineral density or recurrent low-trauma fracture), exclude secondary causes of osteoporosis and/or non-compliance.

A bisphosphonate holiday may be given to patients on oral therapy after a stability of 5 years or on IV therapy after a stability of 3 years in low- to moderate-risk patients. A bisphosphonate holiday is defined as temporary discontinuation of bisphosphonate for up to 5 years or longer depending on the BMD and clinical circumstances of the patient; reassessment of fracture risk is done at 2- to 4-year intervals, and osteoporosis therapy is re-initiated earlier than the 5-year suggested maximum if there is significant reduction in bone mineral density, an intervening fracture, or other factors that changed the patient’s clinical risk status. The American Society for Bone and Mineral Research (ASBMR) Task Force on Long-Term Bisphosphonates has suggested a bisphosphonate holiday for those who have low to moderate fracture risk and switching to another therapy or continuing bisphosphonate in those at high risk. This should be individualized based on benefits and harms of temporary treatment discontinuation.

Initiation of bisphosphonate therapy to reduce fracture risk should be individualized in women >65 years old with osteopenia. Bisphosphonate therapy is associated with a possible risk of osteonecrosis of the jaw and atypical femoral fracture. Oral bisphosphonates should not be given as initial therapy in patients with esophageal diseases, a history of failed compliance with medication intake instructions, and those with chronic renal disease.

Alendronic Acid

Alendronic acid is used in the prevention and treatment of postmenopausal osteoporosis, as it increases BMD and reduces the risk of hip, spinal, and non-vertebral fractures. This is approved for the treatment of osteoporosis in men, as this increases bone mineral density and reduces the risk of spinal fractures. This is approved for the prevention (primary and secondary) and treatment of GIOP in men and women, as it reduces the risk of spinal fractures.

Ibandronic Acid

Ibandronic acid is used in the prevention and treatment of postmenopausal osteoporosis, as it increases BMD and reduces the risk of vertebral fractures.

Risedronic Acid

Risedronic acid is approved for the prevention and treatment of postmenopausal osteoporosis, as it increases BMD and reduces the risk of hip, spinal, and non-vertebral fractures. This may be used in the treatment of osteoporosis in men, as it increases BMD, reduces the risk of hip fractures in men with stroke and concomitant osteoporosis, and reduces the risk of spinal fractures in men with idiopathic osteoporosis. Risedronic acid is used in the prevention (primary and secondary) and treatment of GIOP in men and women, as it reduces the risk of spinal fractures.

Zoledronic Acid

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Zoledronic acid is used in the prevention and treatment of postmenopausal osteoporosis, as it increases BMD and reduces the risk of vertebral, non-vertebral, and hip fractures. This is used in the prevention (primary and secondary) and treatment of GIOP in men and women and should be considered in patients with GIOP who are intolerant to oral bisphosphonates or those with problems with adherence to oral therapy. Zoledronic acid is also indicated in the prevention of new clinical fractures in patients who recently had a low-trauma hip fracture and is also recommended in the prevention and treatment of osteoporosis in women expected to be on glucocorticoid treatment for at least 12 months. A drug holiday may be given to patients on IV therapy following three yearly doses in moderate-risk patients and six yearly doses in high- to very high-risk patients. An anabolic agent or a weaker antiresorptive agent, eg Raloxifene, may be used during the drug holiday.

Hormonal Therapy (HT)¹

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Hormonal therapy is primarily indicated for the treatment of moderate-severe menopausal symptoms (eg vaginal atrophy, vasomotor symptoms) in healthy perimenopausal or menopausal women and for the prevention of osteoporosis, as this increases bone mineral density of the lumbar spine and femoral neck and reduces the risk of vertebral, non-vertebral, and hip fractures. The physician and the patient must consider risk versus benefit before using HT as first-line treatment for the prevention of osteoporosis in women with menopausal symptoms; other treatments should be considered first. When used for treatment of osteoporosis, hormonal therapy should be administered in its lowest effective dose for the shortest duration (2-3 years) due to possible risks; abrupt treatment withdrawal is not recommended. Current data suggests that symptom recurrence is similar when HT is either tapered or abruptly discontinued. Hormonal therapy and Tibolone may be considered in women <60 years of age or postmenopause <10 years, at low risk of deep vein thrombosis (DVT), in whom bisphosphonates or Denosumab is not appropriate, and without breast cancer and history of stroke or myocardial infarction (MI). This may be considered in women >60 years of age who are intolerant to or inappropriate for bisphosphonates or Denosumab and may be considered for prevention of osteoporosis and fractures in women who experience early menopause. Estrogen is not recommended for prevention of fractures in the absence of menopausal symptoms.

Tibolone

Tibolone is a selective tissue estrogenic activity regulator (STEAR) and approved for the prevention of postmenopausal osteoporosis. Data have demonstrated a reduction in vertebral and non-vertebral fractures and improvement of bone mineral density. Tibolone is a synthetic agent that has weak estrogenic, progestogenic, and androgenic properties. This reduces menopausal symptoms, but it does not stimulate uterine or breast tissues.

¹For details on hormonal therapy in menopausal women, please see Menopause and Hormone Therapy disease management chart.

Parathyroid Hormone (PTH) Analogs

Abaloparatide

Abaloparatide is a human PTH-related peptide (PTHrP) analog indicated for the treatment of postmenopausal osteoporosis in women at high risk for fractures and in patients unresponsive or intolerant to other anti-osteoporosis therapy. Studies showed a reduction in vertebral and non-vertebral fractures with long-term treatment (up to 2 years). After completing the treatment course, use of antiresorptive agents (eg bisphosphonates or Denosumab) is recommended to maintain gain in BMD.

Teriparatide (Recombinant human PTH [1-34])

Teriparatide is approved for the treatment of postmenopausal osteoporosis and for men at high to very high risk for fractures and with severe osteoporosis or patients with osteoporosis not responsive to other anti-osteoporosis therapy, as it increases bone mineral density and reduces the risk of spinal and non-vertebral fractures. This is recommended for the prevention of vertebral and non-vertebral fractures in postmenopausal women with severe osteoporosis. Teriparatide has been approved for use for a maximum of 24 months. Follow treatment with a bisphosphonate or other antiresorptive agents (eg Denosumab) to maintain or increase BMD.

Teriparatide is indicated to increase bone mineral density in men with primary or hypogonadal osteoporosis at risk of fracture and may be used in the prevention and treatment of GIOP, as it increases BMD and reduces vertebral fractures. This may reduce the risk of subsequent fractures in patients with prior or prevalent fragility fractures. Teriparatide stimulates new bone formation in cortical and trabecular bone and has anabolic effects on bones.

Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) Inhibitor

Denosumab

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Denosumab is approved for the treatment of osteoporosis in men and postmenopausal women at high risk of fracture and GIOP. This reduces the incidence of vertebral, hip, and non-vertebral fractures and improves bone mineral density. This is also used for the treatment of bone loss in women with breast cancer on aromatase inhibitor treatment, bone loss in men receiving prostate cancer treatments who are at high risk for fracture, and for increasing bone mass in men at high risk of fracture; it may also be used for patients who are intolerant to or have contraindications to or have failed other osteoporosis therapy. Denosumab inhibits the formation, function, and survival of osteoclasts, leading to decreased bone resorption.

A drug holiday is not recommended for patients on Denosumab therapy. Postmenopausal women with osteoporosis who are on Denosumab should be reassessed after 5-10 years for fracture risk, and those who remain at high risk should continue Denosumab or other osteoporosis therapies. Patients with low to moderate risk can be given bisphosphonates followed by a drug holiday with fracture risk reassessed every 1-3 years. Administration should not be delayed or discontinued beyond 7 months without subsequent antiresorptive therapy (eg bisphosphonates, HT, SERM) administered to prevent rebound in bone turnover and to decrease the risk of rapid BMD loss and risk of fracture.

Sclerostin Inhibitor

Romosozumab

Romosozumab is indicated for the treatment of osteoporosis in postmenopausal women at high to very high risk for fracture (ie severe osteoporosis with T-score <-2.5, history of osteoporotic fracture, multiple vertebral fractures, or multiple risk factors for fracture) or those who have failed or are intolerant to other anti-osteoporosis therapy. This reduces vertebral, hip, and non-vertebral fractures. Romosozumab binds to and inhibits sclerostin to increase bone formation and reduce bone resorption. Consider the risks and benefits of therapy prior to initiation due to the potential cardiovascular adverse events. Discontinue therapy if patient experiences a stroke or myocardial infarction (MI). Subsequent use of an antiresorptive agent (eg bisphosphonates or Denosumab) should be considered after 12 monthly doses of Romosozumab to maintain gain in BMD and reduce risk of fracture.

Selective Estrogen Receptor Modulators (SERMs)

Bazedoxifene

Bazedoxifene is used in the prevention and treatment of postmenopausal osteoporosis in women at high risk of fracture. This may be used as monotherapy or in combination with a conjugated estrogen.

Lasofoxifene

Lasofoxifene is a third-generation SERM for the prevention and treatment of postmenopausal osteoporosis with pending approval in the US. This selectively binds to estrogen receptors, thereby reducing the production and lifespan of osteoclasts and stimulating osteoblast activity, with additional effects on calcium homeostasis. Studies showed reduction in vertebral and non-vertebral fractures with long-term treatment.

Raloxifene

Raloxifene is considered a treatment following poor tolerability with first-line agents. This is approved for both prevention and treatment of postmenopausal osteoporosis, as it increases bone mineral density and reduces the risk of vertebral fractures but not non-vertebral fractures. Raloxifene or Bazedoxifene is recommended in women <60 years of age or postmenopause <10 years, at low risk of hip fracture, DVT, and stroke, in whom bisphosphonates or Denosumab are not appropriate, and with a high risk of breast cancer. This may be considered in women >60 years of age who are intolerant to or inappropriate for bisphosphonates or Denosumab.

Raloxifene may be a preferred treatment in women <65 years old without a hip fracture history. This binds to estrogen receptors in target organs to produce various estrogenic effects. If Raloxifene therapy is discontinued, switch to a bisphosphonate to prevent the rapid decline in BMD and to decrease the risk of fracture. Consider the risks and benefits of therapy prior to initiation due to potential VTE events and stroke.

Strontium Ranelate

Strontium ranelate is used for the treatment of severe osteoporosis in postmenopausal women for whom there are no other osteoporotic treatments due to eg contraindications or intolerance. This reduces the risk of vertebral and non-vertebral fractures, reduces the risk of hip fractures in women ≥74 years of age with BMD T-score <-3, and prevents bone loss and vertebral fractures in women with osteopenia.

Strontium ranelate is also used in men for the treatment of severe osteoporosis with increased risk for fracture and is considered an oral alternative for patients with contraindications to or who are intolerant of oral bisphosphonate therapy. This stimulates the formation of new bone tissue and decreases bone resorption as proven in in vitro and experimental studies in animals and long-term clinical studies. Assessment of the risk for cardiovascular disease development should be done prior to treatment and should be monitored every 6-12 months. Treatment should be stopped if the patient develops cerebrovascular disease, ischemic heart disease, uncontrolled hypertension, or peripheral arterial disease.

Activated Vitamin D

Activated vitamin D is used in the treatment of postmenopausal osteoporosis, as it improves BMD and reduces vertebral fracture rate. This is used in the prevention (primary and secondary) and treatment of GIOP. There is BMD improvement, but there is no data to confirm reduction of vertebral fractures. Activated vitamin D regulates the homeostasis of calcium and bone formation. Limit concurrent use of Calcium to <800 mg to decrease the risk of renal stone disease and hypercalcemia.

Calcitonin

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Calcitonin is a thirty-two amino acid hormone secreted by C cells of the thyroid gland. This is approved for the treatment of osteoporosis in women who have been postmenopausal for >5 years and are intolerant of bisphosphonates, hormone-based therapies, Tibolone, SERMs, Denosumab, Abaloparatide or Teriparatide, or when these treatment options are not appropriate, as Calcitonin increases BMD and reduces the risk of spinal fractures. This may be considered in women >60 years of age who are intolerant to or inappropriate for bisphosphonates or Denosumab.

In GIOP, is considered only for patients unable to tolerate oral or IV bisphosphonates or Teriparatide. Calcitonin inhibits osteoclast activity and decreases bone resorption. This has no effect on menopausal symptoms and has an analgesic effect for acute pain relief in osteoporotic fractures. Consider benefits of therapy versus risks, including potential risk for malignancy with long-term use; limit use to <6 months.

Testosterone

Testosterone is suggested in men at borderline high risk for fracture who have serum testosterone levels <200 ng/dL that are accompanied by signs or symptoms of androgen deficiency or organic hypogonadism. This is also suggested in men at high risk for fracture with testosterone levels <200 ng/dL who lack standard indications for testosterone therapy but who have contraindications to approved pharmacological agents for osteoporosis. Many studies have demonstrated that replacement therapy increases bone mineral density in men with hypogonadism; however, effects on fracture reduction are unclear.

Combination Therapy

A combination of a bisphosphonate with a non-bisphosphonate can provide an additional small increase in bone mineral density when compared with monotherapy. A better BMD response is seen with Denosumab and Teriparatide combination therapy than with either agent alone, though there are no available fracture data. SERM Bazedoxifene combined with conjugated estrogen may be considered for the prevention of postmenopausal osteoporosis in patients where other therapies are not appropriate. Added cost and potential increased side effects should be weighed against potential gains.

Other Agents

Genistein

Genistein is a tyrosine kinase inhibitor used in the management of menopausal symptoms. Further studies are needed to prove its benefit on bone health and fracture risk.

Sodium Fluoride (Na Fluoride)

Sodium fluoride stimulates bone formation. Further studies are needed to prove the efficacy of Sodium fluoride in reducing fracture risk. 

Educate all patients on how to reduce the risk of fragility fractures and encourage adherence to drug treatment.

Nutrition

Calcium and Vitamin D

Prevention of Osteoporosis

Lifelong intake of adequate calcium is associated with higher peak bone mass, which reduces the risk of osteoporosis or fracture in later life. Daily supplementation with Calcium and vitamin D is recommended to prevent hip fractures in postmenopausal women at increased risk of fracture with osteoporosis who cannot tolerate bisphosphonates, Denosumab, estrogen, Tibolone, SERM, Abaloparatide and Teriparatide. The recommended calcium intake is 1,000 mg/day for men ≥65 years old and 500-1,200 mg/day for women ≥50 years old. Higher doses may be needed in elderly patients who are homebound or institutionalized or those with conditions that could affect intestinal absorption of calcium (eg achlorhydria, Crohn’s disease, post-bariatric surgery, or use of PPIs). The main sources of calcium are dairy products; vegetables (eg broccoli, cabbage) are also a good source. Vitamin D helps in intestinal calcium absorption, bone mineralization, and enhanced response to bisphosphonate therapy. The recommended vitamin D intake for patients ≥50 years of age: 800-1,000 IU/day. Higher doses may be needed in patients with malabsorption, obesity, older individuals, and transplant patients. A 25 (OH) D blood level of >20 ng/mL is a good index for adequate bone health and vitamin D stores. The main sources of vitamin D are from sun exposure (>15 minutes/day), fortified milk, cereals, egg yolks, saltwater fish, and liver.

Treatment of Osteoporosis

Calcium and vitamin D supplements should be administered as an adjunct to other drug therapies in the treatment of osteoporosis (eg antiresorptive therapy) to decrease the risk of treatment-induced hypocalcemia. Calcium and Vitamin D deficiency should be addressed/treated before initiating osteoporosis treatment. This may be considered in women >60 years of age who are intolerant to or inappropriate for bisphosphonates or Denosumab. This helps to increase BMD and may reduce fracture risk in men and postmenopausal women with osteoporosis.

GIOP

Calcium and vitamin D supplements are recommended for prevention and treatment. These have been shown to reduce bone loss.

Good General Nutrition

Excessive dieting and low body weight are associated with increased risk of fracture. The recommend BMI is ≥19 kg/m². Maintenance of adequate energy and protein intake (US recommended daily allowance [RDA] 0.8 g/kg) and adequate vitamin B, C, E, and K consumption are important as well as consuming a balanced diet.

Dietary Restrictions

Limiting intake of preformed retinol in diet (eg liver, liver products) or as dietary supplements should be considered. The recommended total retinol consumption should be ≤1,500 mcg/day.

Lifestyle Modifications

Exercise 







Regular weight-bearing exercises and muscle-strengthening exercises can improve agility, strength, posture, and balance, which may help to prevent falls. Jogging, brisk walking, tai chi, and weight training may be done. The type of exercise will depend on the age of the patient and physical ability; seek advice from an osteoporosis-trained exercise professional. At least 30 minutes of regular exercise 3-4 times/week is recommended; balance, functional, and resistance training at least twice weekly. Exercise may modestly increase bone density (for as long as exercise is being done). Physiotherapist-guided exercise is recommended for pain reduction and improvement of daily function in patients with painful vertebral fractures.

Avoid Cigarette Smoking and Excessive Alcohol Consumption 







Cigarette smoking and excessive alcohol consumption are associated with increased risk of osteoporotic fractures and should be avoided. Alcohol intake may be limited to <2 units/day.

Limit Caffeine Intake

High caffeine intake (>330 mg/day) increases the risk of fragility fracture. Caffeinated drinks should be limited to <1-2 servings/day (240-360 mL/serving). Patients who regularly consume caffeinated drinks should increase their calcium intake (ie 40 mg Calcium for every 177.5 mL cup of coffee).

Fall Prevention

Individuals with a history of falls should be assessed for fall risk and advised to undergo a DXA scan. Counsel the patient, especially the elderly and those with a history of falls, on ways to reduce risk of falls. Implement measures to prevent falls (eg installing grab bars/handrails, non-slip flooring, adequate lighting, removing loose wires, and keeping things within reach). Hip protectors may help reduce the impact on the hip during a fall. Evaluate for certain medications (eg sedatives, hypnotics, narcotic analgesics, and antihypertensives), neurologic conditions, alcohol use, poor vision and hearing, and frailty and deconditioning, as these may lead to falls. Recommend exercise and physical therapy referral.

Support Devices

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Support devices are recommended for patients with acute vertebral fractures or multiple vertebral fractures associated with chronic pain. Examples of support devices include braces, lumbar corsets, and posture-training support devices. These provide significant pain relief by decreasing the load on fracture sites and realigning the spinal column.

Electrical Stimulation Therapy

Electrical field therapy, with or without exercise, may be considered for pain reduction and improvement of daily function in patients with painful vertebral fractures.