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%)