Update Guidelines of OP

Evaluation & Management

Sattaya Rojanasthien MD
Department of Orthopedics
Faculty of Medicine
Chiang Mai University, Thailand
 Update Guideline 2020
• Reasons to update
1. New drugs available
• Denosumab: RANKL inhibitor
• Romosozumab: antisclerostin provide dual action
• Abaloparatide: parathyroid hormone-related protein analog
2. Strong evidence support higher efficacy of sequential
therapy (anabolic follow by AR)
• Main results (after review of high quality data & expert opinion)
1. Stratify patients into 3 groups
Low-moderate, high, very high risk of fracture
2. Suggest different initial treatment among groups
 Guidelines
• Thai Osteoporosis Foundation (TOPF) position
statement 20161
• IOF-ESCEO 20202
• IOF: The International osteoporosis foundation
• ESCEO: The European Society for Clinical and Economic
Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal
Diseases
• Endocrine Society (global) 20203
• American Academy of Clinical Endocrinologist 20204

1. T. Songpatanasilp, C. Sritara, W. Kittisomprayoonkul, S. Chaiumnuay, H. Nimitphong, N. Charatcharoenwitthaya, C. Pongchaiyakul, S. Namwongphrom,

T. Kitumnuaypong, W. Srikam, P. Dajpratham, V. Kuptniratsaikul, U. Jaisamrarn, K. Tachatraisak, S. Rojanasthien, P. Damrongwanich, W. Wajanavisit, S.
Pongprapai, B. Ongphiphadhanakul, N. Taechakraichana l. TOPF position statement. Osteoporosis and Sarcopenia 2 (2016) 191-207
2. J. A. Kanis, N. C. Harvey, E. McCloskey, O. Bruyère, N. Veronese, M. Lorentzon, C. Cooper, R. Rizzoli, G. Adib, N. Al-Daghri, C. Campusano, M. Chandran,
B. Dawson-Hughes, K. Javaid, F. Jiwa, H. Johansson, J. K. Lee, E. Liu, D. Messina, O. Mkinsi, D. Pinto, D. Prieto-Alhambra, K. Saag, W. Xia,L. Zakraoui, J. -
Y. Reginster. Osteoporos Int (2020) 31:1–12
3. Dolores Schoback, Clifford J. Rosen, Dennis M. Black, Angela M. Cheung, M. Hassan Murad, and Richard Eastell. J Clin Endocrinol Metab 2020
4. Pauline M. Camacho, Steven M. Petak, Neil Binkley , Dima L. Diab, Leslie S. Eldeiry, Azeez Farooki, Steven T. Harris, Daniel L. Hurley, Jennifer Kelly, E.
Michael Lewiecki, Rachel Pessah-Pollack, Michael McClung, Sunil J. Wimalawansa, Nelson B. Watts. ENDOCRINE PRACTICE Vol 26 (Suppl 1) 2020
 IOF-ESCEO Algorithm
for Management of PMO 2020
Infographic plot using absolute major osteoporotic fracture risk (MOF)
of country specific FRAX with respect to age

J.A. Kanis et al. Osteoporos Int (2020) 31:1–12

IOF-ESCEO Algorithm 2020
J.A. Kanis et al. Osteoporos Int (2020) 31:1–12
 Endocrine Society (Global Updated 2020)
High Risk Patients

Criteria • Recent hip or spine fracture

• BMD T-score <-2.5 at hip or spine
• FRAX ≥ 3% hip or ≥ 20% MOF

Treatment • Bisphosphonates
• Denosumab

Reassessment Every 1-3 years by DXA

Comments • Drug holiday included

• Recent fracture is not defined
 Endocrine Society (Global Updated 2020)
Very High Risk Patients
Criteria • Severe or multiple vertebral fractures
• BMD T-score <−2.5 and any fracture(s)
• Bisphosphonate failure (fractures or loss of
BMD while on treatment) or
• ONJ / AFF while on AR

Initial treatment Anabolics

– Teriparatide
– Abaloparatide
– Romosozumab (dual action)

Reassessment Every 1-3 years by DXA

Comments • Imminent fracture risk included

 American Academy of Clinical Endocrinologist (AACE) 2020
High Risk Patients

Criteria • Previous hip or spine fracture (>12 months)

• BMD T-score <−2.5
• FRAX ≥3% (hip) or ≥20% (MOF

Initial Treatment • Bisphosphonates

– Alendronate
– Risedronate
– Zoledronic acid
• Denosumab

Reassessment Every 1-2 years by DXA

Comments Drug holiday for bisphosphonates may be

considered
 American Academy of Clinical Endocrinologist (AACE) 2020
Very High Risk Patients

Criteria • Recent fracture (<12 months)

• Multiple fractures
• Fracture while on approved drug therapy
• Use of drugs that cause skeletal harm
• BMD <−3.0, FRAX >4.5% (hip) or >30% (MOF)
• High fall risk

Initial Treatment • Anabolics (TPTD, Abaloparatide, Romosozumab)

• Denosumab
• Zoledronic acid

Reassessment Every 1-2 years by DXA

Comments Sequential use recommended: anabolic followed by

antiresorptive
 Iceland

• Iceland is a Nordic island country in the North Atlantic Ocean, with

a population of 356,991
• Defined by its dramatic landscape with volcanoes, geysers, hot
springs and lava fields
Most of the population lives in the capital, Reykjavik (เรคยาวิค คยาวิค)
 Imminent Risk of Fracture
Icelandic Reykjavik Study

• A population-based cohort of
18,872 men and women born
between 1907 and 1935 in Iceland
(55% of population in the same age
range)
• Recruitment period 1967-1991
• Median time to FU 28 years until
2012
• Fractures documented in over
510,265 person-years
• 5039 individuals sustained first MOF
• 1919 experienced a second MOF

Helena Johansson et al. Imminent risk of fracture after fracture. Osteoporos Int. 2017
 Imminent Risk of Fracture
after Major Osteoporosis Fracture
Poisson regression
(MOF; i.e., hip, spine, humerus, distal forearm)
Helena Johansson et al. Imminent risk of fracture after fracture. Osteoporos Int. 2017
The risk of a second MOF
• 2.7 (2.4-3.0) fold higher than the
population risk at 1 year
• 1.4 (1.2-1.6) fold after 10 years
• The effect was more marked
with increasing age
• 4% increment risk each year
• 41% higher for women than men
(95% CI: 1.25-1.59).
 Possible Causes of Second Fracture

• Factors that might account for imminent fracture

risk include
• Accelerated rate of bone loss associated with immobility
following a fracture
• Impaired cognitive function with surgery and hospitalization
• Frailty
• Falls
• Adverse effects of medications used in the immediate post-
fracture period

1. Roux C, Briot K. Imminent fracture risk. Osteoporos Int. 2017

2. Helena Johansson, Siggeirsdottir K, Harvey NC, Oden A, Gudnason V, McCloskey E, et al. Imminent risk of
fracture after fracture. Osteoporos Int. 2017
Treatment Sequence Matters
 Antiresorptive Switch to Anabolic

• Total hip BMD effect of switching from potent

antiresorptive to TPTD

Cosman F, Dempster DW. et al. Treatment Sequence Matters: Anabolic and Antiresorptive JBMR 2017
 Alendronate Effective after Anabolic
Therapy (PATH study)
Trabecular hip BMD by QCT

Black DM. NEJM 2005

 Anabolic Switch to Antiresorptive

Cosman F et al. Abaloparatide Followed by Alendronate in ACTIVExtend Trial. Mayo Clin Proc. 2017
 BMD Response: ACTIVExtend Trial

Spine Total hip

Femoral neck

Cosman F et al. Abaloparatide Followed by Alendronate in ACTIVExtend Trial. Mayo Clin Proc. 2017
 Sequence of Therapy
• The sequence of therapy is important [1]
• For patients at very high risk of fracture
– Starting with an osteoanabolic followed by an antiresorptive drug
– To restore degraded skeletal microarchitecture first and then stabilize
and enhance that effect [2, 3]
– If it is not, benefit is likely to be quickly lost [4]
• In contrast, treatment with a potent antiresorptive medication
followed by an osteoanabolic agent may result in delay,
attenuation, or reversal of BMD effects [5, 6]

1. Cosman F, Dempster DW. et al. Treatment Sequence Matters: Anabolic and Antiresorptive JBMR 2017
2. Cosman F et al. Abaloparatide Followed by Alendronate in ACTIVExtend Trial. Mayo Clin Proc. 2017
3. Cosman F et al. Romosozumab Treatment ... N Engl J Med. 2016
4. Black DM et al. One year of alendronate after one year of parathyroid hormone… NEnglJ Med. 2005
5. Obermayer-Pietsch BM et al. Effects of two years of daily teriparatide treatment on BMD… JBMR 2008
6. Leder BZ, Neer RM, et al. Denosumab and teriparatide transitions … Lancet. 2015;386(9999
 Step-Treatment Approach

• The current step-treatment approach mandated by some

payers of healthcare services
• One or two trials of antiresorptive therapy required before
osteoanabolic therapy is allowed, deserves reappraisal
• Starting treatment with an osteoanabolic agent or a
combination of osteoanabolic and antiresorptive therapy may
be preferable in some high risk patients

Cosman F, Nieves JW, Dempster DW. Treatment Sequence Matters: Anabolic and Antiresorptive
Therapy for Osteoporosis. J Bone Miner Res. 2017;32(2):198-202.
Dolores Schoback, Clifford J. Rosen, Dennis M. Black, Angela M. Cheung, M. Hassan Murad, and Richard Eastell. J Clin Endocrinol Metab 2020
 TOPF Indications for
Pharmacological Treatment
postmenopausal osteoporosis (PMO) and male idiopathic osteoporosis (MIO)

1. Vertebral fracture or hip fracture from low-energy injuries

2. Female age >65 years and male aged >70 years with
BMD at lumbar spine or femoral neck or total hip
showing T-score less than -2.5 SD
3. Results from 10-year probability of fracture by FRAX™
using Thai reference (with or without BMD)
3.1 hip fracture ≥ 3%, or
3.2 major osteoporotic fracture ≥20%

Position statement of osteoporosis treatment, TOPF 2016

 Basic Information before Treatment

• To confirm OP and to exclude secondary OP

• Fracture: traumatic or atraumatic
• BMD (total-hip, femoral neck, L1-4, VFA)
• CBC
• BUN, Cr
• Calcium
• LFT (alkaline phosphatase, albumin, globulin)
• PTH
• Thyroid hormone
• Protein electrophoresis, Bence-Jone protein
 Effects of Various Drugs
Beyond OP Treatment
Cancer CV
CV risk
risk Renal
Renal GI Skin
Skin Bone
Bone Others

Estrogen
Estrogen

Calcitonin
Calcitonin

Raloxifene
Raloxifene

Strontium
Strontium
R R

Teriparatide
Teriparatide

Denosumab
Denosumab

BPs
BPs

Romosozumab
 Effects of Various Drugs
Beyond OP Treatment
Cancer CV risk Renal GI Skin Bone Others

Estrogen

Calcitonin

Raloxifene

Strontium R

Teriparatide

Denosumab

BPs

Romosozumab
 Case # 1
• 76-year-old lady got new Colle’s fracture
• Underlying HT, DM, dyslipidemia, senile
dementia, and osteoporosis
• L1-L4 BMD -3.0, Femoral neck BMD -3.2
• Serum Cr 0.9, GFR 35ml/min
• FRAX score (Thai data): hip 3.2%, MOF 24%
What should be an appropriate pharmacologic treatment?
Guideline Initial Treatment
Oral AR Inj AR Anabolic
BP, SERMs, HRT, Zol, Iban, TPTD, Abalo,
VitD analog Dmab Romo

TOPF 2016
Infographic IOF/ESCEO 2020
AACE 2020
Endocrine Society 2020
 Case # 2
• 75-year-old man got hip fracture from a simple fall
• Underlying CKD stage 4
• BMD: right femoral neck was -2.7 SD
• FRAX score (Thai data): hip 4.8%, MOF 22%

Guideline Initial Treatment

Oral AR Inj AR Anabolic
BP, SERMs, HRT, Zol, Iban, TPTD, Abalo,
VitD analog Dmab Romo

TOPF 2016
Infographic IOF/ESCEO 2020
AACE 2020
Endocrine Society 2020
 Case # 3
• 75-year-old lady got a simple fall
• Vertebral compression fracture T12 & L1 & L2
• BMD: L3-L4 was -2.6 SD GFR 35 ml/min
• History of maternal hip fracture
• FRAX score (Thai data): hip 4.2%, MOF 32%
Guideline Initial Treatment
Oral AR Inj AR Anabolic
BP, SERMs, HRT, Zol, Iban, TPTD, Abalo,
VitD analog Dmab Romo

TOPF 2016
Infographic IOF/ESCEO 2020
AACE 2020
Endocrine Society 2020
Case # 4

• 65-year-old lady
• Complain of back pain due to a
simple fall
• T-L spine x-ray as shown
• Hb 8.1, Hct 24.7, plt adequate,
BUN 21, Cr 1.25, eGFR 43
• Total Protein 12.5 (6.6-8.7), Alb
2.3, globulin 10.0 (2.9-3.3)
• Total calcium 7.92 (8.80-10.60)

What is the appropriate management?