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Osteoporosis Treatments and Adverse Events for Osteoporosis Master Class Dr Mary Brown Consultant Rheumatologist 17 May 2019

Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

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Page 1: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Osteoporosis Treatments and Adverse Events

for

Osteoporosis Master Class

Dr Mary BrownConsultant Rheumatologist17 May 2019

Page 2: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline
Page 3: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline
Page 4: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Treatments for osteoporosis• Calcium and vitamin D• (HRT)• Raloxifene• Alendronate• Risedronate• Ibandronate (IV and oral)• IV zoledronate• (Calcitonin)• Calcitriol• Denosumab

• Teriparatide

• (Strontium Ranelate)

Antiresorptives

Anabolic

? action

Page 5: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Treatments for osteoporosis• Calcium and vitamin D• (HRT)• Raloxifene• Alendronate• Risedronate• Ibandronate (IV and oral)• IV zoledronate• (Calcitonin)• Calcitriol• Denosumab

• Teriparatide

• (Strontium Ranelate)

Antiresorptives

Anabolic

? action

Page 6: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Treatments for osteoporosis• Calcium and vitamin D• (HRT)• Raloxifene• Alendronate• Risedronate• Ibandronate (IV and oral)• IV zoledronate• (Calcitonin)• Calcitriol• Denosumab

• Teriparatide

• (Strontium Ranelate)

Antiresorptives

Anabolic

? action

Page 7: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Treatments for osteoporosis• Calcium and vitamin D• (HRT)• Raloxifene• Alendronate• Risedronate• Ibandronate (IV and oral)• IV zoledronate• (Calcitonin)• Calcitriol• Denosumab

• Teriparatide

• (Strontium Ranelate)

Antiresorptives

Anabolic

? action

Page 8: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Treatments for osteoporosis• Calcium and vitamin D• (HRT)• Raloxifene• Alendronate• Risedronate• Ibandronate (IV and oral)• IV zoledronate• (Calcitonin)• Calcitriol• Denosumab

• Teriparatide

• (Strontium Ranelate)

Antiresorptives

Anabolic

? action

Page 9: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Treatments for osteoporosis• Calcium and vitamin D• (HRT)• Raloxifene• Alendronate• Risedronate• Ibandronate (IV and oral)• IV zoledronate• (Calcitonin)• Calcitriol• Denosumab

• Teriparatide

• (Strontium Ranelate)

Antiresorptives

Anabolic

? action

Page 10: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Calcium & Vitamin D

Page 11: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Calcium Calculator

Page 12: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Prescribe a calcium supplementif intake

Ca <1200mg/day

Page 13: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline
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Calcium & Vitamin DConsider:

“caplets” or effervescent Rxs

Vit D alone (Fultium, Stexerol)

high dose Vit D

Page 15: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Calcium & Vitamin DConsider:

“caplets” or effervescent Rxs

Vit D alone (Fultium, Stexerol)

high dose Vit D

Page 16: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Why is compliance so poor?

• Osteoporosis is a silent condition• Patient`s beliefs/perception of fracture

risk• Actual side effects – GI, arthralgia• Fear of potential side effects• Memory impairment• Special requirements for dosing

Page 17: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

“Take the medication 30-60 minutes before breakfast, On an empty stomach with a full

glass of plain tap water; Don`t take any other food, drink

or medications for at least half an hour;

• Remain upright and…….

Patients on oral bisphosphonates are instructed to:

Page 18: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

“Don’t go back to bed or lie down!!”

Page 19: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Bisphosphonates inhibit osteoclast resorption of bone

Page 20: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

82 y/o female23 y/o female

Femoral neck and osteoporosis

Page 21: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

OSTEOPOROTIC BONE

Page 22: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Bone is a living tissue:

Page 23: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Perforation of trabeculae

Presenter
Presentation Notes
Rasterelektronenmikroskopisches Bild eines Osteoklasten Die rasterelektronenmikroskopische Darstellung knöcherner Strukturen zeigt diese in dreidimensionaler Form, hier einen einzelnen Trabekel, dem in seiner Mitte ein Osteoklast aufsitzt. Vorne rechts erkennbar die Grabspuren anderer Osteoklasten. In diesem Bild kann veranschaulicht werden, dass durch die osteoklastäre Resorption nicht nur Knochenmasse abgebaut wird, sondern auch eine Veränderung der Knochenoberfläche entsteht – eine Veränderung der Oberflächenspannung. Diese Veränderung der Oberflächenspannung ist vergleichbar mit dem Anritzen eines Glases mit dem Glasschneider – nach dem Anritzen wird die Festigkeit reduziert. Je mehr derartiger Resorptionslakunen auftreten, um so stärker wird die Festigkeit des Knochens beeinflusst. Die Zahl, Größe und Tiefe der Resorptionslakunen beeinflussen die Festigkeit jedes einzelnen Trabekels. Die roten Dreiecke dokumentieren den Angriffspunkt der Bisphosphonate.
Page 24: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Photo reproduced with permission. © A. Boyde, QMUL.

Osteoclast

Bone Surface Resorbed by Osteoclast

Presenter
Presentation Notes
The osteoclast is the bone lining cell responsible for bone resorption.1 This slide shows an electron micrograph of osteoclast-mediated bone resorption. Baron R. General Principles of Bone Biology. In: Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5th ed. Washington, DC: American Society for Bone and Mineral Research; 2003:1-8.
Page 25: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Patients` biggest fear?

Page 26: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline
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Osteonecrosis of the Jaw (ONJ)• < 1/100,000 pt yrs (in osteoporosis)• ↑ risk with iv bisphosphonates

poor oral hygienediabetescorticosteroidsmalignancy

• N.B. occurs with d`mab, thalidomide & antiVEGF injections and non-osteoporotics

• Dose-related (rather than duration- associated)

Dental check before and during Rx

Page 28: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Atypical Femoral Fractures (AFFs)

Page 29: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

AFFs - Typical Presentation• 0.3 - 1 /1,000 pt yrs • Minimal or no trauma• Noncomminuted• Prodromal thigh pain (64%)• Poor healing (25%)• Bilateral (70%)• >5 yrs bisphosphonate Rx• Assoc. with RA, steroids, PPIs, ↓ Vit D ,

higher BMDShane et al , JBMR 2014

Page 30: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline
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Subtrochanteric Fractures

Page 32: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

STOP BISPHOSPHONATE & XRAY CONTRALATERAL THIGH.

Page 33: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline
Page 34: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

AFFs - PREVENTION

Page 35: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

AFFs - PREVENTION

• Appropriate Rx bisphos. (FRAX score)

(NB 2 atypical #s with denosumab)

• Teriparatide if high fracture risk

• “Drug holidays” for lower risk pts

Page 36: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

DRUG HOLIDAYS

Page 37: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Not all patients should stop bisphosphonates after 5 years.

Page 38: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Drug Holidays• Consider if fracture-free after 5yrs Rx• Review initial indication• Reassess current fracture risk (? T-score >-2.5)

NOT for pts with hip & vertebral #sv. low T-scores>75 yrs + >7.5 mg pred.

P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline 2017

Page 39: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline
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Page 42: Osteoporosis Treatments and Adverse Eventsmedicine.exeter.ac.uk/media/universityofexeter/medical...P9, Executive Summary, Osteoporosis Clinical Guideline, May 2013, NOGG Guideline

Take Home Messages• T score -2.5 does not necessarily mean treatment – do a

FRAX score

• Steroids do not necessarily = a bisphosphonate – do a FRAX score

• Not all patients should stop bisphosphonates after 5 years.

• Investigate thigh pain in patients on long term bisphosphonates