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.