Treatment of Osteoporosis

Bisphosphonates Atypical femur fractures •Stress fractures of the subtrochanteric femur thought to be due to low bone turnover from bisphosphonates •Incidence is 3.2 to 50 per 100,000 patient years but increases with prolonged use •Bisphosphonates cause 1 atypical femur fracture for every 100 typical femur fractures they prevent •Median duration of BP use in patients with atypical fracture is ? •Risk of atypical fractures decreases when BP's are stopped

7 years

Medications for osteoporosis ? agents •Increase bone formation •Because bone formation and bone resorption are coupled bone resorption is also increased

Anabolic

Denosumab Adverse effects Adverse effects •Hypocalcemia -Seen on average 10 days after denosumab -Greater risk in kidney disease, vitamin D deficiency, hypoparathyroidism •Cellulitis •Osteonecrosis of the jaw Monitoring •?

Calcium 10 days after denosumab in patients at high risk of having hypocalcemia

Bisphosphonate Contraindications •Renal insufficiency (GFR < 35 mL/min) •? for oral bisphosphonates •Inability to stay upright for 30 minutes •Hypocalcemia/vitamin D deficiency must be diagnosed/treated before bisphosphates are given

Esophageal disorders

Bisphosphonate Adverse effects •Hypocalcemia •Upper GI side effects (reflux, esophagitis) •Bone/joint pain •? with I.V. •Acute kidney injury •Ocular side effects (rare) •Atypical femur fractures (rare) •Osteonecrosis of the jaw (rare)

Flu-like symptoms

Bisphosphonate Osteonecrosis of the jaw •Exposed mandibular bone in oral cavity •Occurs in 1 in 10,000 to 1 in 100,000 patient years •Occurs more often with ? •Concern is with dental extractions and implants in patients on BP's •Treatment involves stopping BP, antibiotics, mouth rinses, surgery

I.V. bisphosphonates and longer duration of therapy

PTH derivatives Adverse effects •Hypercalcemia •(muscle?) •Osteosarcoma: -Of 300,000 human beings who have used teriparatide there have been 0 confirmed cases of osteosarcoma (1 case has been reported but not confirmed) -Lower than background incidence of osteosarcoma (1 in 250,000)

Muscle pain

•A 56 year old women presents to the emergency department with left thigh pain for the last 5 days. •She denies any recent injury. •Her history of significant for osteoporosis treated with alendronate for the past 8 years. What is the most likely diagnosis?

Subtrochanteric femur fracture

Bisphosphonates Atypical femur fractures •Patients typically present with thigh or groin pain •All patients on BP's with thigh or groin pain should have ? •MRI or bone scan can be done if x-rays are negative but suspicion is still high Treatment •Stop BP •Limited weight bearing •Orthopedic evaluation and possibly surgery

bilateral femur x-rays

Medications for osteoporosis Anabolic agents •Increase ? •Because bone formation and bone resorption are coupled bone resorption is also increased

bone formation

Romosozumab •FDA approved March 2019 •Sclerostin inhibitor •Increases ? •Causes increase in BMD and reduced fractures •May increase risk for cardiovascular disease

bone formation and bone resorption

Bisphosphonates Mechanism of action •Long acting medications that ? •Bind to bone surface •Impairs ability of osteoclast to adhere and dissolve bone •Reduce bone resorption •Also reduce bone formation

deposit in bone

Indications to initiate medications to prevent fracture Osteoporosis •Hip or vertebral fragility fracture •T-score ≤-2.5 in hip or spine Osteopenia (low bone mass) •Must determine ?

fracture risk using FRAX risk assessment to see if treatment is indicated

Bisphosphonate Osteonecrosis of the jaw •Exposed mandibular bone in oral cavity •Occurs in 1 in 10,000 to 1 in 100,000 patient years •Occurs more often with I.V. bisphosphonates and longer duration of therapy •Concern is with dental extractions and implants in patients on BP's •Treatment involves ?

stopping BP, antibiotics, mouth rinses, surgery

Denosumab Advantages •Potent antiresorber •Not as long acting as bisphosphonates •Only has to be given? •Can be used in renal insufficiency unlike bisphosphonate

twice per year

When to restart BP after drug holiday?

•Patient has significant loss of BMD •New fragility fracture

PTH derivatives Uses?

•Patients at highest risk of fracture •Failure/intolerance of other therapies

Bisphosphonates Atypical femur fractures •Stress fractures of the subtrochanteric femur thought to be due to low bone turnover from bisphosphonates •Incidence is 3.2 to 50 per 100,000 patient years but increases with prolonged use •Bisphosphonates cause ? •Median duration of BP use in patients with atypical fracture is 7 years •Risk of atypical fractures decreases when BP's are stopped

1 atypical femur fracture for every 100 typical femur fractures they prevent

PTH derivatives •Teriparatide and abaloparatide •Act on PTH receptor on osteoblast •Intermittent exposure to PTH -Increased osteoclast and osteoblast recruitment resulting in bone formation -Effects trabecular sites (spine) more than cortical sites (forearm and hip) •Continuous exposure to PTH (hyperparathyroidism) causes: -?

Activation of osteoclast leading to bone loss

Medications for osteoporosis ? agents •Stop bone resorption preventing bone loss •Because bone resorption and bone formation are coupled bone formation is also decreased

Antiresorptive

Bisphosphonate Adverse effects •Hypocalcemia •Upper GI side effects (reflux, esophagitis) •? pain •Flue-like symptoms with I.V. •Acute kidney injury •Ocular side effects (rare) •Atypical femur fractures (rare) •Osteonecrosis of the jaw (rare)

Bone/joint

•A 67 year old women presents to primary care clinic for follow-up after undergoing a DXA done as routine screening. •She has no history of fractures and has no other complaints. •She gets 1200 mg of calcium daily from her diet and takes 800 IU of vitamin D daily Her DXA shows a total hip T-score of -2.0 and a lumbar spine T-score -2.1 What is the next step in regards to pharmacotherapy for fracture prevention for this patient?

Calculate her FRAX score to determine whether pharmacotherapy is indicated

Denosumab Adverse effects Adverse effects •Hypocalcemia -Seen on average 10 days after denosumab -Greater risk in kidney disease, vitamin D deficiency, hypoparathyroidism •(skin)? •Osteonecrosis of the jaw Monitoring •Calcium 10 days after denosumab in patients at high risk of having hypocalcemia

Cellulitis

PTH derivatives Adverse effects •(calcium)? •Muscle pain •Osteosarcoma: -Of 300,000 human beings who have used teriparatide there have been 0 confirmed cases of osteosarcoma (1 case has been reported but not confirmed) -Lower than background incidence of osteosarcoma (1 in 250,000)

Hypercalcemia

Bisphosphonate Adverse effects •(calcium)? •Upper GI side effects (reflux, esophagitis) •Bone/joint pain •Flue-like symptoms with I.V. •Acute kidney injury •Ocular side effects (rare) •Atypical femur fractures (rare) •Osteonecrosis of the jaw (rare)

Hypocalcemia

Denosumab Adverse effects Adverse effects •(calcium)? -Seen on average 10 days after denosumab -Greater risk in kidney disease, vitamin D deficiency, hypoparathyroidism •Cellulitis •Osteonecrosis of the jaw Monitoring •Calcium 10 days after denosumab in patients at high risk of having hypocalcemia

Hypocalcemia

Bisphosphonate Contraindications •Renal insufficiency (GFR < 35 mL/min) •Esophageal disorders for oral bisphosphonates •Inability to stay upright for 30 minutes •? must be diagnosed/treated before bisphosphates are given

Hypocalcemia/vitamin D deficiency

Bisphosphonates Atypical femur fractures •Patients typically present with thigh or groin pain •All patients on BP's with thigh or groin pain should have bilateral femur x-rays •? can be done if x-rays are negative but suspicion is still high Treatment •Stop BP •Limited weight bearing •Orthopedic evaluation and possibly surgery

MRI or bone scan

Denosumab Adverse effects Adverse effects •Hypocalcemia -Seen on average 10 days after denosumab -Greater risk in kidney disease, vitamin D deficiency, hypoparathyroidism •Cellulitis •? of the jaw Monitoring •Calcium 10 days after denosumab in patients at high risk of having hypocalcemia

Osteonecrosis

Indications to initiate medications to prevent fractures Postmenopausal women and men over 50 Osteoporosis •Hip or vertebral fractures •T-score ≤-2.5 in hip or spine ? (T-score of -1.0 to -2.4) •FRAX score of ≥3% ten year risk for hip fracture or ≥20% ten year risk for any major osteoporotic fracture

Osteopenia

PTH derivatives Adverse effects •Hypercalcemia •Muscle pain •?: -Of 300,000 human beings who have used teriparatide there have been 0 confirmed cases of osteosarcoma (1 case has been reported but not confirmed) -Lower than background incidence of osteosarcoma (1 in 250,000)

Osteosarcoma

PTH derivatives •Teriparatide and abaloparatide •Act on ? •Intermittent exposure to PTH -Increased osteoclast and osteoblast recruitment resulting in bone formation -Effects trabecular sites (spine) more than cortical sites (forearm and hip) •Continuous exposure to PTH (hyperparathyroidism) causes: -Activation of osteoclast leading to bone loss

PTH receptor on osteoblast

Medications approved for the treatment of osteoporosis Anabolic agents ? •Teriparatide •Abaloparatide Sclerostin inhibitor •Romosozumab

Parathyroid hormone

Bisphosphonate Contraindications •? insufficiency (GFR < 35 mL/min) •Esophageal disorders for oral bisphosphonates •Inability to stay upright for 30 minutes •Hypocalcemia/vitamin D deficiency must be diagnosed/treated before bisphosphates are given

Renal

•A 76 year old male presents to his primary care physician following a recent DXA scan. •He has a history of esophageal cancer which was cured via resection 10 years ago and vertebral compression fracture found scan that was done as part of surveillance for his esophageal cancer. •He takes 1200 mg of calcium and 800 IU of vitamin D via supplementation daily. •His DXA scan shows a total hip T-score of -2.1 and a lumbar T-score of -2.3. What is the next best step in regards to pharmacotherapy for fracture prevention?

Start intravenous zoledronic acid

Bisphosphonates Atypical femur fractures •? thought to be due to low bone turnover from bisphosphonates •Incidence is 3.2 to 50 per 100,000 patient years but increases with prolonged use •Bisphosphonates cause 1 atypical femur fracture for every 100 typical femur fractures they prevent •Median duration of BP use in patients with atypical fracture is 7 years •Risk of atypical fractures decreases when BP's are stopped

Stress fractures of the subtrochanteric femur

Bisphosphonate Adverse effects •Hypocalcemia •? (reflux, esophagitis) •Bone/joint pain •Flue-like symptoms with I.V. •Acute kidney injury •Ocular side effects (rare) •Atypical femur fractures (rare) •Osteonecrosis of the jaw (rare)

Upper GI side effects

Bisphosphonate Administration •Poorly ? •Taken on an empty stomach •Patient should sit or stand for 30 minutes to prevent reflux after taking •Should wait 90 minutes before eating or drinking after taking bisphosphonate •If patient has severe GI symptoms with oral bisphosphonate than an I.V. form can be given

absorbed orally (less than 1%)

Bisphosphonate Administration •Poorly absorbed orally (less than 1%) •Taken on an empty stomach •Patient should sit or stand for 30 minutes to prevent reflux after taking •Should wait 90 minutes before eating or drinking after taking bisphosphonate •If patient has severe GI symptoms with oral bisphosphonate than ?

an I.V. form can be given

Medications for osteoporosis Anabolic agents •Increase bone formation •Because bone formation and bone resorption are coupled ?

bone resorption is also increased

Medications for osteoporosis Antiresorptive agents •Stop ? •Because bone resorption and bone formation are coupled bone formation is also decreased

bone resorption preventing bone loss

Prevention of Bone Loss •1,200 mg of calcium per day either from ? •800 IU of vitamin D3 per day Weight bearing exercise •Walking 30 minutes 3 times per week •Metanalysis has shown a reduction in fractures (4.8% versus 10.9%) •Smoking cessation •Avoidance of excessive alcohol intake

diet or supplements for postmenopausal women

Romosozumab •FDA approved March 2019 •Sclerostin inhibitor •Increases bone formation and bone resorption •Causes increase in BMD and reduced fractures •May ?

increase risk for cardiovascular disease

Selective estrogen receptor modulators •Raloxifene is only SERM approved for osteoporosis in U.S. •Binds to estrogen receptor in bone preventing bone resorption •Prevent vertebral fractures but not hip fractures •Side effects include ? •Reduces risk for invasive breast cancer •Typically only used for osteoporosis when patient can not take other agents or there is a need for breast cancer prevention

increased risk for venous thrombosis and hot flashes

Selective estrogen receptor modulators •Raloxifene is only SERM approved for osteoporosis in U.S. •Binds to estrogen receptor in bone preventing bone resorption •Prevent vertebral fractures but not hip fractures •Side effects include increased risk for venous thrombosis and hot flashes •Reduces risk for ? •Typically only used for osteoporosis when patient can not take other agents or there is a need for breast cancer prevention

invasive breast cancer

Denosumab Advantages •Potent antiresorber •Not as ? •Only has to be given twice per year •Can be used in renal insufficiency unlike bisphosphonate

long acting as bisphosphonates

Denosumab •Receptor activator of nuclear factor kappaB (RANK) ligand which causes osteoclast differentiation and activation •Denosumab is a ? •Potent antiresorptive agent •Given via SQ injection every 6 months Uses •Intolerant of other therapies •Renal dysfunction

monoclonal antibody that binds to RANK ligand thus inhibiting osteoclasts

Denosumab •Receptor activator of ? •Denosumab is a monoclonal antibody that binds to RANK ligand thus inhibiting osteoclasts •Potent antiresorptive agent •Given via SQ injection every 6 months Uses •Intolerant of other therapies •Renal dysfunction

nuclear factor kappaB (RANK) ligand which causes osteoclast differentiation and activation

PTH derivatives •Teriparatide and abaloparatide •Act on PTH receptor on osteoblast •Intermittent exposure to PTH -Increased ? -Effects trabecular sites (spine) more than cortical sites (forearm and hip) •Continuous exposure to PTH (hyperparathyroidism) causes: -Activation of osteoclast leading to bone loss

osteoclast and osteoblast recruitment resulting in bone formation

Bisphosphonates Mechanism of action •Long acting medications that deposit in bone •Bind to bone surface •Impairs ability of ? •Reduce bone resorption •Also reduce bone formation

osteoclast to adhere and dissolve bone

Bisphosphonates Atypical femur fractures •Patients typically present with ? •All patients on BP's with thigh or groin pain should have bilateral femur x-rays •MRI or bone scan can be done if x-rays are negative but suspicion is still high Treatment •Stop BP •Limited weight bearing •Orthopedic evaluation and possibly surgery

thigh or groin pain

PTH derivatives •Teriparatide and abaloparatide •Act on PTH receptor on osteoblast •Intermittent exposure to PTH -Increased osteoclast and osteoblast recruitment resulting in bone formation -Effects ? •Continuous exposure to PTH (hyperparathyroidism) causes: -Activation of osteoclast leading to bone loss

trabecular sites (spine) more than cortical sites (forearm and hip)

FRAX Risk score calculator that includes the following factors?

•Age •Gender •BMI •Previous fragility fracture •Parental history of hip fracture •Smoking •Glucocorticoid use •Rheumatoid arthritis •Alcohol consumption (3 or more units per day) •Femoral neck T-score

PTH derivatives Contraindications to teriparatide?

•Hypercalcemia •Gout •Osteosarcoma or increased risk of osteosarcoma: -Paget's disease -Radiation therapy -Unexplained alkaline phosphatase elevations

Denosumab Disadvantages ?

•Hypocalcemia •Bone loss occurs within 6-12 months of discontinuation •Expensive ($2,000 per year)

Denosumab Adverse effects Adverse effects •Hypocalcemia ? •Cellulitis •Osteonecrosis of the jaw Monitoring •Calcium 10 days after denosumab in patients at high risk of having hypocalcemia

-Seen on average 10 days after denosumab -Greater risk in kidney disease, vitamin D deficiency, hypoparathyroidism

Monitoring of osteoporosis treatment •Repeat DXA is generally recommended every ? •Expect stability or slight increase in BMD on antiresorptive therapy

1-2 years after starting therapy

Bisphosphonate drug holiday •Most suggest stopping BP's after ? Rationale •Allow bone turnover to increase •Decrease risk for atypical femur fractures and ONJ •Antifracture effects persist after stopping BP's because they are long acting meds which deposit in bone

3-10 years in most patients

Bisphosphonate Administration •Poorly absorbed orally (less than 1%) •Taken on an empty stomach •Patient should sit or stand for 30 minutes to prevent reflux after taking •Should wait ? •If patient has severe GI symptoms with oral bisphosphonate than an I.V. form can be given

90 minutes before eating or drinking after taking bisphosphonate

Bisphosphonate Adverse effects •Hypocalcemia •Upper GI side effects (reflux, esophagitis) •Bone/joint pain •Flue-like symptoms with I.V. •? injury •Ocular side effects (rare) •Atypical femur fractures (rare) •Osteonecrosis of the jaw (rare)

Acute kidney

Romosozumab •FDA approved March 2019 •Sclerostin inhibitor •Increases bone formation and bone resorption •Causes increase in ? •May increase risk for cardiovascular disease

BMD and reduced fractures

Medications approved for the treatment of osteoporosis Antiresorptive agents ? •Alendronate •Risedronate •Ibandronate •Zoledronic acid RANK ligand inhibitors •Denosumab Selective estrogen receptor modulators (SERMs) •Raloxifene

Bisphosphonates

? •Receptor activator of nuclear factor kappaB (RANK) ligand which causes osteoclast differentiation and activation •Denosumab is a monoclonal antibody that binds to RANK ligand thus inhibiting osteoclasts •Potent antiresorptive agent •Given via SQ injection every 6 months Uses •Intolerant of other therapies •Renal dysfunction

Denosumab

•A 75 year old women presents to her primary care physician 2 months after fracturing her right femoral neck for routine follow-up. •DXA scan is performed and shows a total hip T-score of -2.8 and a lumbar spine T-score of -3.0. •Her past medical history is significant for breast cancer 10 years ago status post mastectomy and radiation therapy. She also has hypertension and chronic kidney disease. •She gets 1,200 mg/day from her diet and is on 1,000 IU of vitamin D daily. •Routine lab work shows reduced renal function. What is the best treatment for this patient?

Denosumab

Bisphosphonate Osteonecrosis of the jaw •(what is it)? •Occurs in 1 in 10,000 to 1 in 100,000 patient years •Occurs more often with I.V. bisphosphonates and longer duration of therapy •Concern is with dental extractions and implants in patients on BP's •Treatment involves stopping BP, antibiotics, mouth rinses, surgery

Exposed mandibular bone in oral cavity

Bisphosphonate Adverse effects •? (up to 25% of pt.'s) •Esophageal cancer •Hypocalcemia -1.2% of patients receiving zoledronic acid -9-11 days after •Flu-like symptoms with I.V. zoledronic acid •Renal impairment

GERD, esophagitis, ulcers

Medications approved for the treatment of osteoporosis Antiresorptive agents Bisphosphonates •Alendronate •Risedronate •Ibandronate •Zoledronic acid ? •Denosumab Selective estrogen receptor modulators (SERMs) •Raloxifene

RANK ligand inhibitors

Denosumab •Receptor activator of nuclear factor kappaB (RANK) ligand which causes osteoclast differentiation and activation •Denosumab is a monoclonal antibody that binds to RANK ligand thus inhibiting osteoclasts •Potent antiresorptive agent •Given via ? Uses •Intolerant of other therapies •Renal dysfunction

SQ injection every 6 months

Romosozumab •FDA approved March 2019 •? inhibitor •Increases bone formation and bone resorption •Causes increase in BMD and reduced fractures •May increase risk for cardiovascular disease

Sclerostin

Medications approved for the treatment of osteoporosis Anabolic agents Parathyroid hormone •Teriparatide •Abaloparatide ? •Romosozumab

Sclerostin inhibitor

Medications approved for the treatment of osteoporosis Antiresorptive agents Bisphosphonates •Alendronate •Risedronate •Ibandronate •Zoledronic acid RANK ligand inhibitors •Denosumab ? •Raloxifene

Selective estrogen receptor modulators (SERMs)

Denosumab •Receptor activator of nuclear factor kappaB (RANK) ligand which causes osteoclast differentiation and activation •Denosumab is a monoclonal antibody that binds to RANK ligand thus inhibiting osteoclasts •Potent ? •Given via SQ injection every 6 months Uses •Intolerant of other therapies •Renal dysfunction

antiresorptive agent

Monitoring of osteoporosis treatment •Repeat DXA is generally recommended every 1-2 years after starting therapy •Expect stability or slight increase in BMD on ?

antiresorptive therapy

Medications for osteoporosis Antiresorptive agents •Stop bone resorption preventing bone loss •Because bone resorption and bone formation are coupled ?

bone formation is also decreased

Bisphosphonates Mechanism of action •Long acting medications that deposit in bone •Bind to bone surface •Impairs ability of osteoclast to adhere and dissolve bone •Reduce ? •Also reduce bone formation

bone resorption

Bisphosphonate Osteonecrosis of the jaw •Exposed mandibular bone in oral cavity •Occurs in 1 in 10,000 to 1 in 100,000 patient years •Occurs more often with I.V. bisphosphonates and longer duration of therapy •Concern is with ? •Treatment involves stopping BP, antibiotics, mouth rinses, surgery

dental extractions and implants in patients on BP's

FRAX •Developed by World Health Organization •Was designed to be easy to use by everyone •Uses over 1 million patient years worth of data from several large studies to calculate 10-year risk of hip fracture and major osteoporotic fracture •Generally done to ?

determine if a patient with osteopenia (low bone mass) should be treated with a medication to prevent fracture

ndications to initiate medications to prevent fractures Premenopausal women and men under 50 •Most of these patients have secondary osteoporosis •Management should focus on ? •Medications to prevent fractures may sometimes be used but there is less evidence to guide management in this population

diagnosing and treating the underlying cause of bone loss

Selective estrogen receptor modulators •Raloxifene is only SERM approved for osteoporosis in U.S. •Binds to ? •Prevent vertebral fractures but not hip fractures •Side effects include increased risk for venous thrombosis and hot flashes •Reduces risk for invasive breast cancer •Typically only used for osteoporosis when patient can not take other agents or there is a need for breast cancer prevention

estrogen receptor in bone preventing bone resorption

Bisphosphonates Atypical femur fractures •Stress fractures of the subtrochanteric femur thought to be due to low bone turnover from bisphosphonates •Incidence is 3.2 to 50 per 100,000 patient years but ? with prolonged use •Bisphosphonates cause 1 atypical femur fracture for every 100 typical femur fractures they prevent •Median duration of BP use in patients with atypical fracture is 7 years •Risk of atypical fractures decreases when BP's are stopped

increases

Selective estrogen receptor modulators •Raloxifene is only SERM approved for osteoporosis in U.S. •Binds to estrogen receptor in bone preventing bone resorption •Prevent vertebral fractures but not hip fractures •Side effects include increased risk for venous thrombosis and hot flashes •Reduces risk for invasive breast cancer •Typically only used for osteoporosis when?

patient can not take other agents or there is a need for breast cancer prevention

Estrogen replacement for osteoporosis •Does effectively reduce vertebral and hip fractures •Is appropriate for use in premenopausal women with estrogen deficient •Not approved for treatment of osteoporosis in ?

postmenopausal women due to increased risk of breast cancer and venous thrombosis

Estrogen replacement for osteoporosis •Does effectively reduce vertebral and hip fractures •Is appropriate for use in ? •Not approved for treatment of osteoporosis in postmenopausal women due to increased risk of breast cancer and venous thrombosis

premenopausal women with estrogen deficient

ndications to initiate medications to prevent fractures Premenopausal women and men under 50 •Most of these patients have secondary osteoporosis •Management should focus on diagnosing and treating the underlying cause of bone loss •Medications to ? may sometimes be used but there is less evidence to guide management in this population

prevent fractures

Bisphosphonates Mechanism of action •Long acting medications that deposit in bone •Bind to bone surface •Impairs ability of osteoclast to adhere and dissolve bone •Reduce bone resorption •Also ?

reduce bone formation

Denosumab Advantages •Potent antiresorber •Not as long acting as bisphosphonates •Only has to be given twice per year •Can be used in ?

renal insufficiency unlike bisphosphonate

Indications to initiate medications to prevent fractures Premenopausal women and men under 50 •Most of these patients have ? •Management should focus on diagnosing and treating the underlying cause of bone loss •Medications to prevent fractures may sometimes be used but there is less evidence to guide management in this population

secondary osteoporosis

Bisphosphonate Administration •Poorly absorbed orally (less than 1%) •Taken on an empty stomach •Patient should ? •Should wait 90 minutes before eating or drinking after taking bisphosphonate •If patient has severe GI symptoms with oral bisphosphonate than an I.V. form can be given

sit or stand for 30 minutes to prevent reflux after taking

Bisphosphonate Contraindications •Renal insufficiency (GFR < 35 mL/min) •Esophageal disorders for oral bisphosphonates •Inability to ? •Hypocalcemia/vitamin D deficiency must be diagnosed/treated before bisphosphates are given

stay upright for 30 minutes

Selective estrogen receptor modulators •Raloxifene is only SERM approved for osteoporosis in U.S. •Binds to estrogen receptor in bone preventing bone resorption •Prevent ? •Side effects include increased risk for venous thrombosis and hot flashes •Reduces risk for invasive breast cancer •Typically only used for osteoporosis when patient can not take other agents or there is a need for breast cancer prevention

vertebral fractures but not hip fractures

Prevention of Bone Loss •1,200 mg of calcium per day either from diet or supplements for postmenopausal women •800 IU of ? Weight bearing exercise •Walking 30 minutes 3 times per week •Metanalysis has shown a reduction in fractures (4.8% versus 10.9%) •Smoking cessation •Avoidance of excessive alcohol intake

vitamin D3 per day

Bisphosphonates Atypical femur fractures •Stress fractures of the subtrochanteric femur thought to be due to low bone turnover from bisphosphonates •Incidence is 3.2 to 50 per 100,000 patient years but increases with prolonged use •Bisphosphonates cause 1 atypical femur fracture for every 100 typical femur fractures they prevent •Median duration of BP use in patients with atypical fracture is 7 years •Risk of atypical fractures decreases ?

when BP's are stopped

Bisphosphonate drug holiday •Most suggest stopping BP's after 3-10 years in most patients Rationale ?

•Allow bone turnover to increase •Decrease risk for atypical femur fractures and ONJ •Antifracture effects persist after stopping BP's because they are long acting meds which deposit in bone

PTH derivatives Disadvantages ?

•Daily injection •Can only be used for 2 years •Bone loss will occur after teriparatide is stopped •Relatively expensive ($ 6720 per year) •Anabolic effects are not as efficacious when used after antiresorptive agents like BP's

Treatment failures •A subsequent vertebral fracture on therapy is reduced by 80-90% When patients have a fracture or marked reduction in BMD (5%) on 2 serial measurements on therapy: ?

•Evaluate compliance •Evaluate for causes of secondary osteoporosis •Some would consider bone biopsy of labs are unremarkable

Indications to initiate medications to prevent fracture Osteoporosis ? Osteopenia (low bone mass) •Must determine fracture risk using FRAX risk assessment to see if treatment is indicated

•Hip or vertebral fragility fracture •T-score ≤-2.5 in hip or spine

Denosumab •Receptor activator of nuclear factor kappaB (RANK) ligand which causes osteoclast differentiation and activation •Denosumab is a monoclonal antibody that binds to RANK ligand thus inhibiting osteoclasts •Potent antiresorptive agent •Given via SQ injection every 6 months Uses ?

•Intolerant of other therapies •Renal dysfunction

PTH derivatives Advantages ?

•Only anabolic agent •No concerns about long term effects on bone turnover (i.e. atypical fractures, ONJ) •Limited data about hip fracture prevention

Prevention of Bone Loss •1,200 mg of calcium per day either from diet or supplements for postmenopausal women •800 IU of vitamin D3 per day Weight bearing exercise •Walking 30 minutes 3 times per week •Metanalysis has shown a reduction in fractures (4.8% versus 10.9%) (social factors)?

•Smoking cessation •Avoidance of excessive alcohol intake

Bisphosphonates Atypical femur fractures •Patients typically present with thigh or groin pain •All patients on BP's with thigh or groin pain should have bilateral femur x-rays •MRI or bone scan can be done if x-rays are negative but suspicion is still high Treatment ?

•Stop BP •Limited weight bearing •Orthopedic evaluation and possibly surgery

Prevention of Bone Loss •1,200 mg of calcium per day either from diet or supplements for postmenopausal women •800 IU of vitamin D3 per day Weight bearing exercise ? •Smoking cessation •Avoidance of excessive alcohol intake

•Walking 30 minutes 3 times per week •Metanalysis has shown a reduction in fractures (4.8% versus 10.9%)