sarena ravi md, mph endocrinologist · 2019. 9. 26. · women >65 and men >70 (regardless of...
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Sarena Ravi MD, MPH
Endocrinologist
Franciscan Physicians Network
Division of Endocrinology
Chicago, IL
Definition & Diagnosis of Osteoporosis
Management of Osteoporosis in all Populations
Long term Management of Osteoporosis
Characterized by low bone mass
Micro-architectural Disruption
Increased Skeletal Fragility
Influenced and affected by
bone mineral density
rates of bone resorption and formation (turnover)
bone geometry (size and shape of bone)
microarchitecture
Cortical and Trabecular
Bone
Cortical Bone
• 80% of all the bone in the body
• 20% of Bone Turnover
Trabecular Bone
• 20% of all bone in the body
• 80% of Bone Turnover
T-score <= -2.5 SD’s at any site based upon BMD measurement by dual-energy x-ray absorptiometry (DXA)
Fragility Fracture!
Particularly at the spine, hip, wrist, humerus, rib, and pelvis
Commonly missed – FRAGILITY fracture means Osteoporosis
BMD assessment by DXA does not apply in presence of fragility fracture
A T-score that is 1 to 2.5 SD below the young adult mean is termed low bone mass (osteopenia)
Normal bone density is defined as a value within 1 SD of the mean value in the young adult reference population
There are actually more fractures in patients with a T-score between -1 and -2.5 because there are so many more patients in this category
Bone Fractures which occur spontaneously or from minor trauma
Spine, hip, wrist, humerus, rib, and pelvis
Clinical diagnosis of Osteoporosis can be made without BMD
Fragility fracture result from mechanical forces that would not ordinarily result in fracture:
Fall from a standing height or less Bending, vacuuming, picking up something, coughing and sneezing,
walking, daily chores, ect… Unknown – fracture is incidentally found on imaging
57 year old, post-menopausal female Referred to me for thyroid lab abnormality – autoimmune hyperthyroidism During Chart Review – saw imaging fro 2012 reported “vertebral compression
fracture” DXA scan T-scores were not <= -2.5 (did not report osteoporosis) Was told “probably early stages of osteoporosis” and did not initiate treatment or
refer to specialist Patient herself recalls feeling sudden pain in her back that year while vacuuming
(no trauma)
Is this Osteoporosis? YES!!
In setting of fragility fracture – BMD/T-score does not apply!
Should this be treated? YES!!
Initiated treatment with IV Zolendronic Acid
Reference population in which the T-score -2.5 SDs below the mean were standardized to were young, Caucasian females
Currently extrapolated to older Men > age 50
Above definition of osteoporosis based on population of Caucasian Females
WHO does not have enough data to create definitions for Men or other Ethnic Groups
Even in setting of fragility fracture – DXA may not be able to report osteoporosis
Above Criteria cannot be used in Pre-menopausal women and Men <50
Cannot be used in children
WHO:
“…all cut-off values are somewhat arbitrary, but a measured value of bone mineral more than 2.5 standard deviations below the mean for young healthy women at any site (spine, hip, mid-radius) identifies 30 % of all postmenopausal women as having osteoporosis, more than half of whom will have sustained a prior fracture of the proximal femur, spine, distal forearm, proximal humerus or pelvis.”
Other reasons DXA findings not always accurate:
Positioning and errors by technician
Variability in machine – same machine should be used each time
Errors in demographic reporting (age, ect…)
Wrong scan mode, invalid skeletal site, inability to report LSC, artifacts, arthritis, ect
T-Score
WHO Criteria should NOT be applied to Pre-Menopausal women or Men <50
Relationship between BMD and fracture risk is not the same in younger women/men
Z-Score
Comparison of the patients BMD to an age-matched population
-2 or below is considered below expected range for age
Coexisting problems should be investigated such as alcoholism and steroid therapy
Applied in Children, Men <50, and Pre-Menopausal women
Who should be screened for Osteoporosis?
National Osteoporosis Foundation (NOF):
Women >65 and Men >70 (regardless of clinical RF)
Younger Postmenopausal women, women in menopausal transition, and men age 50-69 with clinical risk factors
Adults with fragility fracture >50 years
Adults with underlying chronic conditions (eg RA), chronic glucocorticoid use, or other pharmaceutical therapies associated with low BMD
AACE
Similar to NOF
Any adult with a fragility fracture
No recommended guidelines for men
Clinical Risk Factors & Secondary Causes of Osteoporosis that support early screening:
(Women <65, Pre-menopausal, Men 50-69, Men <50)
Drugs:
Glucocorticoids, Immunosuppressants, Anti-seizure, GnRH agonists/antagonists, Heparin, Chemotherapy
GI/Nutrition:
Liver disease, Chronic cholestasis, Gastrectomy/GI Surgeries, Malabsorption, Pancreatic disorder, Vit D/Ca deficiency
Endocrine:
Cushing’s, Acromegaly, Adrenal Insufficiency, Eating Disorders, Hyperparathyroidism, Hyperthyroidism, Hyperprolactinemia, Hypogonadism, DM
Clinical Risk Factors & Secondary Causes of Osteoporosis that support early screening:
(Women <65, Pre-menopausal, Men 50-69, Men <50)
Marrow Related Disorders:
Hemochromatosis, Multiple Myeloma, Sarcoidosis, SSA/Thalassemia, Lymphoma, ect
Organ Transplantation
Misc/Genetic:
Hemophilia, Idiopathic Hypercalciuria, Ankylosing spondylitis, MS, RA, OI
Who should be treated?
Management Varies: Post-Menopausal Females and Men > 50T-score and BMD used to guide treatment/management
WHO criteria on T-score should be used
Pre-Menopausal Females and Men < 50WHO criteria on T-score should NOT be used
Relationship between BMD and fracture not the same in younger men/women
Z-Scores (esp children)
Lifestyle measurements & Fall precautions
Smoking, Alcohol, Exercise, Diet, Hip Protectors
Calcium + Vitamin D
Pharmacological Therapy:
Bisphosphonates: Anti-resorptive therapy
Reduce activity of bone-resorbing Osteoclasts
Alendronate, Ibandronate, Risedronate, and Zoledronic Acid
Denosumab: Anti-resorptive therapy
Decreases formation, differentiation, of Osteoclasts and decreases function of active Osteoclasts
Raloxifene
Teriparatide/Abaloparatide
”Anabolic agent”
T-Score <= -2.5 at any site (AACE)
Total hip, Femoral Neck, Lumbar Spine, 33% (1/3rd) or Radius
Even in the absence of prevalent fracture
Osteopenia (T-Score between -1.0 and -2.5) if Fracture Risk is High!
Chronic Glucocorticoid Use
High Frax Score
Fragility Fracture!!
Regardless of T-score
Osteopenia with high FRAX Score Treat same way as osteoporosis!
FRAX Score 10-year probability for Major osteoporotic fracture and Hip fracture >= 20% for Major Treatment with pharmacologic therapy >= 3% for Hip Treatment with pharmacologic therapy
Age, height, weight, family history, parent with hip fx, prior fracture, smoking, alcohol use, secondary causes, RA, steroid use, ethnicity, BMD at femoral neck, type of DXA machine
All these factors used to calculate FRAX Score
Calculation tool where we enter the date score is then given
Does not apply when T-score <= -2.5 or if Fragility Fracture
Already Osteoporosis!
Does not apply to patients already being treated for Osteoporosis
Indicate patient’s RISK for Fracture
Low – Mild – Moderate – High
Management Varies
LOW Risk Osteopenia
No pharmacological treatment
Lifestyle measures, Ca, Vitamin D, Fall Precaution
MILD Risk Pharmacological Therapy
Osteopenia with high FRAX Score/High Fracture Risk
Initiate with Bisphosphonates (if no C/I)
Treat for 3-5 years (IV/PO)
DXA/BMD every 1-2 years
Increasing or stable Initiate Drug Holiday
End Drug Holiday and Re-Initiate Pharmacological Therapy if:
Fragility Fracture
Significant Decline in BMD based LSC
Moderate Fracture Risk Osteoporosis Per WHO Criteria for T-score
No Prior Fragility Fracture, No chronic steroid therapy, T-score not severely low
Pharmacological Therapy
Bisphosphonates or Denosumab
DXA every 1-2 years Increasing or stable BMD Drug Holiday
Resume Therapy If:
Fragility fracture
Significant Decline in BMD
Bone Turnover Markers rise to pre-treatment levels
Resume therapy 3-5 years after drug holiday
Moderate Fracture Risk Osteoporosis Per WHO Criteria for T-score
No Prior Fragility Fracture, No chronic steroid therapy, T-score not severely low
Pharmacological Therapy
Bisphosphonates or Denosumab
DXA every 1-2 years Decrease in BMD or Fragility Fracture
Assess Compliance
Re-evaluate for Secondary Causes!
Switch to Injectable if on PO
Switch to Anabolic agent (Teriparatide) if on Injectable
High Fracture Risk Prior Fragility Fracture
Advanced Age, Frailty, Glucocorticoids, Very Low T-Scores, Fall Risk
Pharmacological Therapy
Teriparatide/Abaloparatide, Denosumab, Zoledronic Acid
DXA /BMD yearly or every 1-2 years
Denosumab Continue therapy (Drug holiday?)
Significant Decline in BMD Teriparatide or anabolic agent
Teriparatide (Anabolic) - Only up to 2 years max
Sequential Therapy with oral/IV antiresorptive agent!
BMD begins to decline after ending therapy
Zoledronic Acid
Continue for 6 years
Significant Decline in BMD Anabolic Agent (Teriparatide)
Lifestyle changes (diet, smoking, alcohol, ect…)
Calcium + Vitamin D (adequate dietary and supplemental intake)
FDA Approved Therapy:
Alendronate, Risedronate, Zoledronic Acid
Hip Fracture Zoledronic Acid
Ibandronate not approved
Teriparatide (Abaloparatide only for post-menopausal females)
Denosumab only for men receiving ADT for prostate cancer
Not YET been shown to prevent fracture in other men
Used in clinical practice still does have beneficial effect on BMD
Intolerant to other therapies or Impaired Renal Function
HYPOGONADISM and OSTEOPOROSIS For men at high risk of fracture and on testosterone therapy
Add agent with proven anti-fracture efficacy (e.g. a bisphosphonate or teriparatide).
Men at borderline/moderate high risk for fracture with hypogonadism
Testosterone therapy in lieu of a “bone drug”
After 2 years of testosterone therapy BMD T-score <-2.5
Add Established Osteoporosis therapy
If Testosterone therapy contraindicated Osteoporosis therapy
Contraindications to all approved Osteoporosis therapy
Suggest testosterone therapy for men at high risk for fracture
If established hypogonadism
Secondary Causes!!
BMD/DXA Testing in these populations if:
History of Fragility Fracture
Diseases, conditions, or medications associated with low bone mass/bone loss
Considering pharmacologic therapy for osteoporosis
Monitoring Drug Therapy for Osteoporosis
Women in Menopausal Transition if RF are present
Low body weight, prior low-trauma fracture, high risk medications, ect…
Secondary Causes!!
Management Ca + Vitamin D (diet + supplements)
Weight Bearing Exercises/Lifestyle changes (smoking, alcohol, nutrition…)
Treatment of Secondary Causes! Not the same as post-menopausal or men > 50
Pharmacologic Treatment in Selected Cases
Refer to Specialist!! Endocrine, Rheumatology, University Center, Specialized Bone
Center, ect…
Table 11
Causes of Secondary Osteoporosis in Adults
Endocrine or metabolic causes Nutritional/GI conditions Drugs Disorders of collagen metabolism Other
Acromegaly
Diabetes mellitus
Type 1
Type 2 Growth
hormone
deficiency
Hypercortisolism
Hyperparathyroidism
Hyperthyroidism
Hypogonadism
Hypophosphatasia
Porphyria
Pregnancy
Alcoholism Anorexia
nervosa
Calcium deficiency
Chronic liver disease
Malabsorption
syndromes/
malnutrition
(including celiac
disease, cystic
fibrosis, Crohn’s
disease, and gastric
resection or bypass)
Total parenteral
nutrition
Vitamin D deficiency
Antiepileptic drugsa
Aromatase inhibitors
Chemotherapy/
immunosuppressants
Depo-Provera
Glucocorticoids
Gonadotropin-releasing
hormone agents
Heparin
Lithium
Proton pump inhibitors
Selective serotonin
reuptake
inhibitors
Thiazolidinediones
Thyroid hormone (in
supraphysiologic doses)
Ehlers-Danlos syndrome
Homocystinuria due to
cystathionine deficiency
Marfan syndrome
Osteogenesis
imperfect
AIDS/HIV
AS
COPD
Gaucher disease
Hemophilia
Hypercalciuria
Immobilization
Major depression
Myeloma and some
cancers
Organ transplantation
Renal insufficiency/
failure
Renal tubular acidosis
Rheumatoid arthritis
Systemic
mastocytosis
Thalassemia
All Populations with Osteoporosis/Low BMD:
CBC/CMP/Phos
PTH
TSH
Vitamin D levels
Celiac
SPEP/UPEP
Test for Cushing’s If Clinically Suspicious
24 Hr Urinary Calcium Suspicion of malabsorption, Kidney stones, PTH disorder, Bariatric/GI surgeries
More Extensive Testing/Secondary Workup:
Pre-Menopausal Females and Men <50
Post-Menopause and Men >50 If Suspicious Clinical Features Present
Ca + Vitamin D Supplementation or Adequate Dietary Intake
Men > 50 and Post-Menopausal Females Treat if Osteoporosis Present
Any dose or duration of GC
Men > 50 and Post-Menopausal Females Osteopenia and High risk
Treat with Pharmacological Therapy
Any dose or duration of GC Therapy
All Other Men > 50 and Post-Menopausal Females
Prednisone >= 7.5 mg/day or Equivalent for greater than 3 months
Treat with Pharmacological Therapy For Prevention
Men < 50 and Pre-Menopausal Females
Hypogonadism, Fragility Fracture, Z-Scores, Accelerated Bone Loss on DXA
Individualized to Patient Refer Specialist
Refer to Endocrinology, Rheumatology, University Bone Clinic…
Pre-menopausal females & Men < 50 Management is Different!
Secondary Causes MUST be Investigated and Treated’
Pediatric Population and Very Young Men/Women
Post-Menopausal Women and Men > 50 Chronic management requires experience reading DXA images, BMD
comparisons using LSC, Knowledge on Contraindications and SE of Osteoporosis Therapy
Chronic management by same provider(s) crucial for appropriate long term care
May not have access to prior DXA’s for comparisons
Patients may not know prior treatments or remember where they were treated
Also may now know what years and duration they were treated for osteo
Decisions on terminating or continuing Drug Holidays will be difficult
Osteoporosis and Chronic Kidney Disease (CKD)
Risk for CKD-MBD (Mineral Bone Disease)
Renal Osteodystrophy: Adynamic Bone Disease & Osteomalacia
Underproduction of Bone Cannot treat with Osteoporosis Therapy
Bisphosphonates not recommended in GFR < 35
Specialized Bone Centers may still administer them
Anabolic Agents (Forteo & Tymlos)
Must be used with caution Risk of 2ndary Hyper-PTH in CKD
Denusomab can possibly used in GFR < 30
Not recommended due to risk of Hypocalcemia
Very Close Monitoring
Underproduction of Bone Cannot treat with Osteoporosis Therapy
All cases should have close monitoring by multiple specialists including Nephrology
When taking history from New Patients…
“I took Fosamax for 1-2 years…was told to stop because it wasn’t working”
“I took Fosamax for 12 years”
“I believe I’ve been on Fosamax, and Boniva for a few years, and also Actonel”
“I’m not sure when my last DXA scan was, or where I had it, or who my doctor was at the time”
“I had a compression fracture, DXA was normal so was never treated”
“I took Fosamax from in my late 30’s – early 40’s”
“I’ve been on Prolia for few years…no never seen Nephrology”
(Female pt with GFR in the 30’s)
“I’ve been on Fosamax for more than 5 years, I was told to continue it”
GFR declined to 20’s (Diabetic Nephropathy)
When taking history from New Patients…
“I took Fosamax for 1-2 years…was told to stop because it wasn’t working”
“I took Fosamax for 12 years”
All Bisphosphonates and Denosumab have a recommended length of treatment before a Drug Holiday
Improvements should be assessed over a 3-10 year period – not just 1-2 years
“I believe I’ve been on Fosamax, and Boniva for a few years, and also Actonel”
Makes it difficult to decide on terminating or continuing a Drug Holiday
“I’m not sure when my last DXA scan was, or where I had it, or who my doctor was at the time”
Without prior DXA/BMD, cannot compare to recent numbers
Stability vs. Significant Changes in BMD helps determine further management
When taking history from New Patients…
“I had a vertebral fracture…DXA was normal so was never treated”
First Case: Fragility fracture Osteoporosis!!
“I took Fosamax from in my late 30’s – early 40’s”
How was Osteoporosis diagnosed? (Z-score or T-score?)
Secondary work up??
“I’ve been on Prolia for few years…no never seen Nephrology”
Female pt with GFR in the 30’s
Risk for Adynamic Bone Disease should be assessed
“I’ve been on Fosamax for several years, I was told to continue it”
GFR declined to 20’s (Diabetic Nephropathy)
Bisphosphonates should not be used GFR < 35
Referred to me for uncontrolled IDDM with hypoglycemia in setting of CKD
Chart Review: Osteoporosis diagnosed in 2011 (T-score) Never Treated
2011-2018: Multiple (3) Vertebral fractures developed
2017-2018 GFR declined from 50’s to 20’s
Significant Chronic Back Pain, Severe decline in mobility, Impaired Ambulationwith Inability to do Several Daily Activities
Compression fractures led to Central Canal compromise with Spinal Cord Compression
Transferred to University Hospital for Neurosurgery management
Post-Discharge Months of Rehab
GFR Decline from 50’s to 20’s in 1 year (2017-2018)
Treatment BEFORE Decline in GFR would have been greatly beneficial
Untreated Osteoporosis & Overlooking Fragility Fractures
Very Debilitating for patient Increased Morbidity
Significant Increases in Cost
MAJOR POINTS Fragility Fracture Osteoporosis!
Long Term Management
Contraindications in therapy (eg GFR..)
Dx of Osteoporosis Begin Therapy
Commonly Overlooked
Secondary Work-up
Pre-Menopausal Females and Men < 50
More in depth Secondary work up!
Osteopenia with High Risk Treat as Osteoporosis!
Chronic Glucocorticoids Assess Fracture Risk
Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis - AACE/ACE Postmenopausal Osteoporosis CPG. Camacho, Pauline M et al Endocr Pract. 2016;22(Suppl 4)
Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline. Watts, Nelson B et al. The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 6, 1 June 2012, Pages 1802–1822.
2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Buckley L, et al. Arthritis Rheumatol. 2017;69(8):1521. Epub 2017 Jun 6.
Factors related to variation in premenopausal bone mineral status: a health promotion approach. Tudor-Locke C, McColl RS SO Osteoporos Int. 2000;11(1):1.
Epidemiology and clinical features of osteoporosis in young individuals.AUKhosla S, Lufkin EG, Hodgson SF, Fitzpatrick LA, Melton LJ 3rd SO Bone. 1994;15(5):551.
Low bone mass in premenopausal parous women: identification and the effect of an information and bone density feedback program. AUJones G, Scott F SOJ Clin Densitom. 1999;2(2):109.
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