Osteoporosis Treatment

• Choice of drug will depend not only on its capacity to increase BMD but also on reducing spine and hip fracture
• Therapy should be initiated without delay (2 weeks or more after a hip fracture) based on fracture risk in patients with recent fractures to prevent more fractures
  • Fracture within the past 2 years is a better predictor of imminent fracture risk (fracture within the next 2 years) than a distant fracture (>5 years ago)
• Postmenopausal women and men ≥50 years old with the following should be considered for treatment:
  • Low-trauma hip, vertebral or wrist fracture
  • T-score of ≤-2.5 at the femoral neck, total hip, lumbar spine, or 33% radius by DXA
  • Low bone mass (T-score between -1.0 and -2.5 at the femoral neck, lumbar spine, total hip, or 33% radius by DXA, osteopenia) and 10-year FRAX™ fracture probability of ≥3% at the hip or ≥20% for major osteoporosis-related fracture at 10 years
• On discontinuing glucocorticoids, treatment in continued similar to non-glucocorticoid osteoporosis for those with confirmed or high risk for osteoporosis
• Switching from antiresorptive therapy (bisphosphonates, Denosumab, hormonal therapy [HT], selective estrogen receptor modulators [SERMs], Strontium ranelate) to osteoanabolic (bone formation) therapy (Teriparatide, Abaloparatide, Romosozumab) is considered in the following:
  • Postmenopausal women with osteonecrosis of the jaw or atypical femoral fracture on antiresorptive therapy
  • Postmenopausal women with recurrent vertebral fractures due to osteoporosis
  • Postmenopausal women at high to very high fracture risk and on long-term potent antiresorptive therapy and sustaining fractures

• 1st-line of treatment for osteoporotic patients to reduce the risk of fracture and patients receiving glucocorticoids with osteoporotic fractures or established osteoporosis
  • Can be considered for prevention of bone loss in postmenopausal women with T-score of <-1 and other risk factors for fracture who do not fulfill criteria for osteoporosis treatment 
• Inhibits osteoclast activity and potent inhibitors of bone resorption
• Have no effect on menopausal symptoms
• Evaluate efficacy of treatment after 3 years on intravenous (IV) therapy and 5 years on oral therapy
  • If ineffective (ie declining BMD or recurrent low-trauma fracture), exclude secondary causes of osteoporosis and/or noncompliance
• 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 5-year suggested maximum if there is significant reduction in BMD, an intervening fracture or other factors that changed the patient’s clinical risk status
  • American Society for Bone and Mineral Research (ABSMR) Task Force on Long-Term Bisphosphonates has suggested bisphosphonate holiday for those who have low to moderate fracture risk and switching to another therapy or continuing bisphosphonate in those at high risk
  • 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 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, history of failed compliance with medication intake instructions and those with chronic renal disease

• Used in the prevention and treatment of postmenopausal osteoporosis
  • Increases BMD, reduces risk of hip, spinal and non-vertebral fractures

• Approved for the treatment of osteoporosis in men
  • Increases BMD, reduces risk of spinal fractures

• Approved for the prevention (primary and secondary) and treatment of GIOP in men and women
  • Reduces risk of spinal fractures

• Used in the prevention and treatment of postmenopausal osteoporosis
  • Increases BMD, reduces risk of vertebral fractures 

• Approved for the prevention and treatment of postmenopausal osteoporosis
  • Increases BMD, reduces risk of hip, spinal and non-vertebral fractures

• May be used in the treatment of osteoporosis in men
  • Increases BMD
  • Reduces the risk of hip fractures in men with stroke and concomitant osteoporosis
  • Reduces the risk of spinal fractures in men with idiopathic osteoporosis

• Used in the prevention (primary and secondary) and treatment of GIOP in men and women
  • Reduces risk of spinal fractures

• Used in the prevention and treatment of postmenopausal osteoporosis
  • Increases BMD, reduces the risk of vertebral, non-vertebral and hip fractures
• Used in the prevention (primary and secondary) and treatment of GIOP in men and women
  • Should be considered in patients with GIOP who are intolerant to oral bisphosphonates or those with problems with adherence to oral therapy
• Also indicated in the prevention of new clinical fractures in patients who recently had a low-trauma hip fracture
• 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 3 yearly doses in moderate-risk patients and 6 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

• Primarily indicated for treatment of moderate-severe menopausal symptoms (eg vaginal atrophy, vasomotor symptoms) in healthy perimenopausal or menopausal women and for the prevention of osteoporosis
  • Increases BMD of lumbar spine and femoral neck, reduces risk of vertebral, non-vertebral and hip fractures
  • Physician and patient must consider risk versus benefit before using hormonal therapy as 1st-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 due to possible risks; abrupt treatment withdrawal is not recommended
  • Current data suggests that symptom recurrence is similar when hormonal therapy 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) 
  • May be considered in women >60 years of age who are intolerant to or inappropriate for bisphosphonates or Denosumab
• 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
• For details on hormonal therapy in menopausal women, please see Menopause & Hormone Therapy disease management chart

Tibolone

• A selective tissue estrogenic activity regulator (STEAR)
• Approved for the prevention of postmenopausal osteoporosis
  • Data have demonstrated a reduction in vertebral fracture and non-vertebral fractures and improvement of BMD
• Synthetic agent which has weak estrogenic, progestogenic and androgenic properties
• Reduces menopausal symptoms but it does not stimulate uterine or breast tissues

Parathyroid Hormone (PTH) Analogs

Abaloparatide 

• 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 reduction in vertebral and non-vertebral fractures with long-term treatment (up to 2 years)
• After completing treatment course, use of antiresorptive agents (eg bisphosphonates or Denosumab) is recommended to maintain gain in BMD 

Teriparatide (Recombinant human PTH [1-34])

• 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
  • Increases BMD, reduces risk of spinal and non-vertebral fractures
• Recommended for the prevention of vertebral and non-vertebral fractures in postmenopausal women with severe osteoporosis 
• 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
• Indicated to increase BMD in men with primary or hypogonadal osteoporosis at risk of fracture
• May be used in the prevention and treatment of GIOP
  • Increases BMD, reduces vertebral fractures
• Stimulates new bone formation in cortical and trabecular bone
• Has anabolic effects on bones
• A trial has shown that Teriparatide reduces fractures more than Risedronate

• Approved for the treatment of osteoporosis in men, postmenopausal women at high risk of fracture and GIOP
  • Reduces the incidence of vertebral, hip and non-vertebral fractures and improves BMD
• 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; may also be used for patients who are intolerant to or have contraindications to or failed other osteoporosis therapy
• Inhibits formation, function and survival of osteoclasts leading to a decreased bone resorption
• A drug holiday is not recommended to patients on Denosumab therapy
• Postmenopausal women with osteoporosis and 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

• 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 
  • Reduces vertebral, hip and non-vertebral fractures 
• 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 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 

• Used in the prevention and treatment of postmenopausal osteoporosis in women at high risk of fracture 
• May be used as monotherapy or in combination with a conjugated estrogen

Lasofoxifene

• A 3rd-generation SERM for the prevention and treatment of postmenopausal osteoporosis with pending approval in the US
• Selectively binds to estrogen receptors thereby reducing the production and lifespan of osteoclasts, stimulation of osteoblast activity, with additional effects on calcium homeostasis
• Studies showed reduction in vertebral and non-vertebral fractures with long-term treatment

Raloxifene 

• Considered as treatment following poor tolerability with 1st-line agents
• Approved for both prevention and treatment of postmenopausal osteoporosis
  • Increases BMD, reduces 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 is not appropriate, and with a high risk of breast cancer
  • May be considered in women >60 years of age who are intolerant to or inappropriate for bisphosphonates or Denosumab 
• May be a preferred treatment in women <65 years old without a hip fracture history
• 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 

• Used for treatment of severe osteoporosis in postmenopausal women for whom there are no other osteoporotic treatments due to eg contraindications or intolerance
  • 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
  • Prevents bone loss and vertebral fractures in women with osteopenia
• Also used in men for the treatment of severe osteoporosis with increased risk for fracture 
• Considered as an oral alternative for patients with contraindications to or are intolerant of oral bisphosphonate therapy
• 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 risk for cardiovascular disease development should be done prior to treatment and should be monitored every 6-12 months
  • Treatment should be stopped if patient develops cerebrovascular disease, ischemic heart disease, uncontrolled hypertension or peripheral arterial disease

Activated Vitamin D

• Used in the treatment of postmenopausal osteoporosis
  • Improves BMD and reduces vertebral fracture rate
• Used in the prevention (primary and secondary) and treatment of GIOP
  • BMD improvement but no data to confirm reduction of vertebral fractures
• 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

• 32 amino acid hormone secreted by C cells of the thyroid gland
• Approved for the treatment of osteoporosis in women who have been postmenopausal for >5 years and intolerant of bisphosphonates, hormone-based therapies, Tibolone, SERMs, Denosumab, Abaloparatide or Teriparatide, or when these treatment options are not appropriate
  
  • Increases BMD, reduces risk of spinal fractures
• 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
• Inhibits osteoclast activity and decreases bone resorption
• Has no effect on menopausal symptoms
• Has 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

• Suggested in men at borderline high risk for fracture who have serum testosterone levels <200 ng/dL that is accompanied by signs or symptoms of androgen deficiency or organic hypogonadism
• Also suggested in men at high risk for fracture with testosterone levels <200 ng/dL who lacks standard indications for testosterone therapy but who have contraindications to approved pharmacological agents for osteoporosis
• Many studies have demonstrated that replacement therapy increases BMD in men with hypogonadism, however, effects on fracture reduction are unclear

• Combination of a bisphosphonate with a non-bisphosphonate can provide additional small increase in BMD when compared with monotherapy
• A better BMD response is seen with Denosumab and Teriparatide combination therapy than 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 

• 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)

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

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/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 
  • Recommended calcium intake: 1000 mg/day for men ≥65 years old; 1200 mg/day for women ≥50 years old
  • 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 enhance response to bisphosphonate therapy
  • Recommended vitamin D intake for patients >50 years of age: 800-1000 IU/day
    • Higher doses may be needed in patients with malabsorption, obesity, older individuals, transplant patients
  • 25 (OH) D blood levels 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, salt water fish and liver

• Treatment of osteoporosis
  • Calcium and Vitamin D supplements should be administered as adjunct to other drug therapies in the treatment of osteoporosis (eg antiresorptive therapy) to decrease the risk of treatment-induced hypocalcemia
  • May be considered in women >60 years of age who are intolerant to or inappropriate for bisphosphonates or Denosumab
  • Help to increase BMD and may reduce fracture risk in men and postmenopausal women with osteoporosis

• Glucocorticoid-induced osteoporosis
  • Recommended for prevention and treatment
  • Has been shown to reduce bone loss

Good General Nutrition 

• Excessive dieting and low body weight is associated with increased risk of fracture
  • Recommend BMI ≥19 kg/m²
• Maintenance of adequate energy and protein intake (US RDA 0.8 g/kg) and adequate vitamin B, C, E and K consumption are is 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; recommended total retinol consumption should be ≤1500 mcg/day

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

Support Devices

• Eg braces, lumbar corset, posture-training support devices
• Recommended for patients with acute vertebral fractures or multiple vertebral fractures associated with chronic pain
• Provides significant pain relief by decreasing the load on fracture sites and realigning the spinal column