MANAGEMENT OF

SECONDARY OSTEOPOROSIS

Awalia

Sub-bagian Rematologi Dept./SMF Ilmu Penyakit Dalam

FK UNAIR – RSUD Dr. Soetomo Surabaya
 Secondary osteoporosis is defined as low bone
mass with microarchitectural deterioration leading to
fragility fractures in the presence of underlying
disease or medication.
 It is a challenge in diagnosis and therapy, as it
frequently affects premenopausal women or younger
men. The underlying conditions are diverse, often
rare and require specialized tests for diagnosis.

Ebeling PR. Secondary causes of osteoporosis: Bone diseases. In: Osteoporosis, diagnosis
and management. Stovall DW (Ed.). 2013. John Wiley & sons Ltd. London.
Hofbauer LC, Hamann C, Ebeling PR. Approach to the patient with secondary osteoporosis.
European Journal of Endocrinology (2010) 162 1009–1020
Hofbauer LC, Hamann C, Ebeling PR. Approach to the patient with secondary osteoporosis.
European Journal of Endocrinology (2010) 162 1009–1020
Algorhitm for identifying causes of secondary OP
Bone KW. Recognizing and treating secondary osteoporosis. Nat .Rev. Rheumatol 8, 480 (2012)
 9

Indications For Bone Density Testing

• All women age 65 and older
• All men age 70 and older
• Adults with a fragility fracture
• Adults with a disease or condition associated with low bone
density
• Adults taking medication associated with low bone density
• Anyone being treated for low bone density to monitor
treatment effect
• Anyone not receiving therapy, in whom evidence of bone
loss would lead to treatment

Women discontinuing treatment should be considered for bone density

testing according to the indications listed above.

ISCD Position Development Conference 2003

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Using T-scores vs. Z-scores

T-scores Z-scores
• WHO diagnositic • For use in reporting BMD
classification in in healthy premenopausal
postmenopausal women women, men under age
and men age 50 and 50, and children
older • Z-score -2.0 or less is
• WHO classification with defined as “below the
T-score cannot be applied expected range for age”
to healthy premenopausal • Z-score above -2.0 is
women, men under age “within the expected
50, and children range for age”
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Z-score
Patient’s BMD – Age-Matched Mean BMD
1 SD of Age-Matched Mean BMD
Low Z-score (less than -2.0) has been suggested
by some to increase likelihood of secondary
osteoporosis, however . . .
– This is not validated in clinical trials
– High index of suspicion for secondary causes of
osteoporosis is recommended for all patients
Z-score  2 : below expexted range of age
Z-score > 2 : within expexted range of age
Dx OP utk pre-M women cant be made based on BMD alone
Bone turnover marker:
Not for dx OP  predictor fr & Mx tx response

Marker bone resorption:

- N- telopeptide (NTX) serum/urine
- C-telopeptide (CTX) serum/urine
- Deoxypyridinoline (DPO) urine

Marker bone formation:

- BSAP (bone specific AlkP)
- Osteocalcin
- PINP (prokolagen-type I N-terminal propeptide)
Management of secondary osteoporosis aims to:
(1) treat the underlying disease, and
(2) increasing bone mass to prevent future
fractures.

A practical approach with patient-centered,

individualized therapy is warranted.
Endocrine diseases
 Cushing’s syndrome & primary hyperparathyroidism
should be surgically treated if osteoporosis (+)
 Hyperthyroidism should be treated with drugs,
radioiodine, or surgery
 Sex hormones deficiency should be replaced if OP (+)
 DM pts need prevention of nephropathy, retinopathy,
neuropathy to prevent falls
Gastrointestinal diseases
 Restoration or maintenance of normal BW.
 Celiac disease: gluten-free diet.
 IBD: Use immunosuppressant/biologic agent to
control inflammation & reduce steroid dose
 After GI surgery: monitor calcium and vitamin D level
for life.
Drug usage needs to be evaluated and changed, e.g:
 Local/nasal steroid preferred to systemic
 After transplantation & for DMARDs, use other than
calcineurin inhibitor (cyclosporine A) & steroids.
 TZDs should be changed with other insulin sensitizer
 Heparin can be changed to oral vit K antagonist
 Monitor thyroid function test (overshoot will ↓ BMD)
Drug usage needs to be evaluated and changed, e.g:
 Low dose TCAs is better than SSRIs for fracture risk
 Use anticonvulsant not affect vit D/Ca metabolism.
 H2-blockers are better than PPIs for fracture risk.
 Choose contraception other than Depo-progesterone
 Tamoxifen is preferred than AIs (anastrozole/letrozole)

Bowles SK. Drug-induced osteoporosis. Women’s and Men’s Health. PASP VII. 2010
Effects of treatments on various diseases
Ferrari S, et al. Osteoporosis of young adults: pathophysiology, diagnosis, and management. Osteoporosis Int (2012) 23:2735
 The most common cause of secondary OP
 1% of US population is treated with long-term GCs
 > 10% have fracture, 30-40% have
radiographic evidence of vertebral fracture
Fracture risk categories in GC-treated pts
2017 ACR Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporois
 Non-pharmacologic

 Pharmacologic
Bone Health Building Blocks
 Bone KW. Recognizing and
treating secondary osteoporosis.
Nat .Rev. Rheumatol 8, 480 (2012)
 Calcium Intake Recommendations
Estimated Recommended Dietary Upper Level Intake
Life Stage Group Requirement (mg/day) Allowance (mg/day) (mg/day)
Infants 0 to 6 months * * 1,000
Infants 6 to 12 months * * 1,500
1–3 years old 500 700 2,500
4–8 years old 800 1,000 2,500
9–13 years old 1,100 1,300 3,000
14–18 years old 1,100 1,300 3,000
19–30 years old 800 1,000 2,500
31–50 years old 800 1,000 2,500
51–70 year-old male 800 1,000 2,000
51–70 year-old female 1,000 1,200 2,000
>70 years old 1,000 1,200 2,000

* For infants, adequate intake is 200 mg/day for 0 to 6 months of age and 260 mg/day for 6 to 12 months of age.

Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D: Report Brief. Washington, DC: IOM ; 2010.
Available at: http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed
September 13, 2013.
 Vitamin D Intake Recommendations
Estimated Avg Recommended Upper Level Intake
Requirement Dietary Allowance (IU/day)
Life Stage Group (IU/day) (IU/day)
Infants 0 to 6 months * * 1.000
Infants 6 to 12 months * * 1,500
1–3 years old 400 600 2,500
4–8 years old 400 600 3,000
9–13 years old 400 600 4,000
14–18 years old 400 600 4,000
19–30 years old 400 600 4,000
31–50 years old 400 600 4,000
51–70-year-old male 400 600 4,000
51–70-year-old female 400 600 4,000
>70 years old 400 600 4,000

* For infants, adequate intake is 400 IU/day for 0 to 6 months of age and 400 IU/day for 6 to 12 months of age.

Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D: Report Brief. Washington, DC: IOM; 2010.
Available at: http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed
September 13, 2013.
BONE MASS HOMEOSTASIS

Harada S, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature 2003;423:349-55
FDA-Approved Therapeutic Options

Prevention Treatment

Estrogen Calcitonin
Alendronate
Risedronate
Ibandronate
Zoledronic acid
Raloxifene
PTH (teriparatide)
Denosumab
Drugs approved by FDA for treatment of OP
Osteoporosis Algorithm

Hamdy RC. Algorithm for management of osteoporosis. Southern Medical Journal 2010, 103 :1009
Drugs approved by FDA for prevention of OP
 Bisphosphonates
Alendronate, Risedronate, Ibandronate, and Zoledronic Acid

• Alendronate: 10 mg daily (tablet) or 70 mg weekly (tablet or

liquid) for treatment, 5 mg daily or 35 mg weekly for
prevention

• Risedronate: 5 mg daily or 35 mg weekly (tablet); 150 mg

monthly (tablet)

• Ibandronate: 150 mg monthly by tablet; 3 mg intravenously

over 15 to 30 seconds every 3 months

• Zoledronic acid: 5 mg by intravenous infusion over a

minimum of 15 minutes once every year for treatment—and
every other year for prevention

National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National
*
Osteoporosis Foundation; 2013. Available at: http://www.nof.org/hcp/clinicians-guide. Accessed September 13, 2013.
2012 Jun 25;172(12):930-6
 Bisphosphonates
Contraindications/Warnings/Precautions
– Hypocalcemia
– Creatinine clearance <30 cc/min (<35 cc/min for zoledronic acid)
– For oral dosing: Esophageal stricture or impaired esophageal motility (alendronate);
inability to stand or sit for at least 30 minutes (alendronate/risedronate) or 60
minutes (ibandronate)
Notes: UGI symptoms per se are not a contraindication to oral dosing.
Use in pregnancy: Class C
Oral dosing requirements
– Tablets (with exception of delayed release risedronate) taken on an empty stomach
after overnight fast with 6 to 8 oz of plain water while in an upright position
– Patients should not eat or lie down for at least 30 minutes (alendronate
and risedronate) or 60 minutes (ibandronate)
– Calcium and vitamin D supplements, if needed, should be taken at a different time
of day than the oral bisphosphonate

National Osteoporosis Foundation. Med Lett. 2011;53(1360):24.

 Bisphosphonate Holidays
• In patients at high risk for fractures, continued treatment
seems reasonable. Consider a drug holiday of 1 to 2 years
after 10 years of treatment

• For lower risk patients, consider a “drug holiday” after 4 to 5

years of stability

• Follow BMD and bone turnover markers during a drug holiday

period, and reinitiate therapy if bone density declines or
markers increase

Watts NB et al; AACE Osteoporosis Task Force. Endocr Pract. 2010;16(Suppl 3):1-37.
Whitaker M, et al. N Engl J Med. 2012;366(22):2048-2051.
 Teriparatide: rhPTH [1-34]
• The only treatment agent that is anabolic—stimulates bone
formation rather than inhibiting bone resorption
• 20 μg daily (subcutaneously) for no more than 2 years
• Indication: treatment of men and postmenopausal women
with osteoporosis who are at high risk for fracture
• Effects:
– Increased bone density in spine by 9% and hip by
3% vs placebo over 18 months
– Reduced incidence of vertebral fractures (65%) and
nonvertebral fragility fractures (53%) in women with
pre-existing vertebral fractures
– Studies too small to evaluate effect on hip fractures
• Adverse reactions: arthralgia, pain, nausea; warning about
osteosarcoma risk in rats
Neer RM, et al. N Engl J Med. 2001;344:1434-1441.
Forteo (prescribing information). Indianapolis, IN: Eli Lilly and Company; March 21, 2012.
 Osteoporosis drugs efficacy

Compston J. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteopor (2017) 12:43
Thank You