1. Osteoporosis Dima L. Diab, MD, FACE, FACP, CCD
Associate Professor of Medicine
Division of Endocrinology, Diabetes and Metabolism
University of Cincinnati College of Medicine
Bone Health and Osteoporosis Center
Metabolic Bone Diseases and Mineral Disorders 1

2. Osteoporosis Definition: NIH Consensus Conference1
A skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture
Bone strength = Bone quantity (BMD) + Bone quality
Osteoporotic bone2
Normal bone
1 NIH Consensus Statement March 2000
2 JBMR 1986; 1:15-21

3. World Health Organization (WHO) Diagnostic Criteria
The WHO Study Group, 1994

4. T-scores and Z-scores
Areal bone mineral density (BMD) is expressed in absolute terms of grams of mineral per square centimeter scanned (g/cm2) and as a relationship to two norms:
compared to a young-adult reference population (T-score),
compared to the BMD of an age-, sex-, and ethnicity-matched reference population (Z-score).
A Z-score of -2.0 or lower is considered abnormally low for a person’s age, sex and race.

6. Secondary Osteoporosis Evaluation
Careful history and examination
Laboratory testing (minimum):
CBC
Complete metabolic panel (including Cr, Ca, phos, alkaline phosphatase, LFT’s)
25-OH vitamin D
24-hr urine calcium, sodium and creatinine
Testosterone (in men)
Identifies ~90% of occult disorders at a reasonable cost
JCEM 2002;87:

7. Additional Testing In Selected Patients
TSH if symptomatic, elderly or on treatment
PTH
SPEP, UPEP, immunofixation / light chains
24-hr urine free cortisol
estradiol (in premenopausal women with oligo- or amenorrhea)
celiac disease abs
iron studies if hemochromatosis is suspected
testing for mastocysis (histamine metabolites)
testing for HIV
BTM’s
bone biopsy in rare cases

8. Indications for DXA testing NOF Clinician’s Guide
Consider BMD testing in the following individuals:
Women age 65 and older and men age 70 and older, regardless of clinical risk factors
Younger postmenopausal women, women in the menopausal transition, and men age 50 to 69 with clinical risk factors for fracture
Adults who have a fracture at or after age 50
Adults with a condition (e.g. RA) or taking a medication (e.g. glucocorticoids) associated with low bone density or bone loss
NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis 2014

9. FRAX®: WHO Fracture Risk Assessment Tool
Developed by WHO to evaluate fracture risk of patients from data from NA, Europe, Australia, Asia
Integrates clinical risk factors and femoral neck BMD
Estimates 10-year patient-specific absolute fracture risk
Hip
Major osteoporotic fracture (spine, forearm, hip, or humerus)
>3%
>20% 9

10. Clinical Risk Factors Included in the FRAX Tool

12. Glucocorticoids (oral at a dose of 5 mg/d predn or higher for more than 3 months)

13. FRAX Example

14. FRAX Benefits
BMD + CRFs predict fracture risk better than BMD or CRFs alone
Can be used without BMD when DXA is not available
Quantitative assessment of fracture risk

15. FRAX Limitations Does not apply to premenopausal patients
Does not apply to treated patients
Does not include all risk factors
Important risk factors not considered
(falls, BTMs, etc.)
Yes or No response to CRFs does not consider range of risk (e.g. smoking, alcohol)
May underestimate or overestimate fracture risk
Does not quantify risk factors; e.g.:
3 personal pelvis fractures = 1 ankle fracture
5 mg prednisone for 3 months 2 years ago = 60 mg prednisone daily now
BMD input limited to femoral neck
Cannot use BMD of the spine or forearm 15 15

16. Approved Therapies for Osteoporosis
Antiresorptive Agents
Anabolic Agents
Calcitonin
Raloxifene (SERM)
Bisphosphonates
- Alendronate
- Risedronate
- Ibandronate
- Zoledronic acid
Denosumab (RANKL ab)
Teriparatide (PTH 1-34)
Abaloparatide (PTHrP analog) 16

17. Case 1
A 70-year-old woman falls and sustains a fracture of her right hip. She takes calcium supplementation but no other supplements or medications.
Physical examination is unremarkable.
A dual energy x-ray absorptiometry (DXA) scan reveals a T-score of -3.4 in the left femoral neck.

18. Laboratory studies show the following:
Calcium 8.7 mg/dL (normal, )
Phosphorus 3.0 mg/dL (normal, )
PTH 80 pg/mL (normal, )
25-(OH) D 8 ng/mL (normal, )
1,25-(OH)2 D 50 pg/mL (normal, )
Albumin 3.8 g/dL (normal, )
Urinary calcium 30 mg/24 hours (normal, )

19. Question #1 Which of the following should be recommended initially?
Vitamin D
Raloxifene
Alendronate
Denosumab
Teriparatide

20. Answer #1 Which of the following should be recommended initially?
A. Vitamin D
This patient has severe vitamin D deficiency which needs to be treated before any other pharmacologic intervention for osteoporosis.
Her 25-hydroxyvitamin D level is extremely low, in single digits, and has resulted in hypocalciuria and secondary hyperparathyroidism. A diagnosis of osteomalacia should be considered in this clinical scenario.
B. Raloxifene
C. Alendronate
D. Denosumab
E. Teriparatide

21. Which of the following should be recommended initially?
A. Vitamin D
B. Raloxifene
C. Alendronate
D. Denosumab
E. Teriparatide
All the other listed options (answers B, C, D, and E) are approved therapies for osteoporosis and would not be the best initial treatment for this patient.
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96:

22. Case 1 (cont’d)
She was treated with vitamin D, and repeat laboratory studies several months later revealed the following:
25-(OH) D 34 ng/mL (normal, )
Calcium 9.8 mg/dL (normal, )
Albumin 4.2 g/dL (normal, )
PTH 60 pg/mL (normal, )
Creatinine 0.9 mg/dL (normal, )
Urinary calcium 150 mg/day (normal, )

23. Case 1 (cont’d)
A repeat DXA scan a year later reveals a T-score of -2.6 in the left femoral neck.
Upon further questioning, she reports history of breast cancer s/p radiation therapy and history of DVT.
She also reports difficulty swallowing due to an esophageal stricture.

24. Question #2 Which of the following would you recommend to treat her osteoporosis at this time?
Raloxifene
Alendronate
Zoledronic acid
Teriparatide
No treatment is necessary at this time

25. Answer #2
Which of the following would you recommend to treat her osteoporosis at this time?
A. Raloxifene
B. Alendronate
C. Zoledronic acid
Zoledronic acid (an intravenous bisphosphonate) as the best treatment option for this patient’s osteoporosis.
D. Teriparatide
E. No treatment is necessary at this time

26. Which of the following would you recommend to treat her osteoporosis at this time?
A. Raloxifene
Raloxifene (a SERM) is associated with an increased risk of VTE.
B. Alendronate
Alendronate (an oral bisphosphonate) should be avoided in view of her esophageal stricture.
C. Zoledronic acid
D. Teriparatide
E. No treatment is necessary at this time

27. Which of the following would you recommend to treat her osteoporosis at this time?
A. Raloxifene
B. Alendronate
C. Zoledronic acid
D. Teriparatide
Teriparatide (recombinant PTH) is contraindicated in patients who have had radiation therapy to the skeleton.
E. No treatment is necessary at this time
This patient has osteoporosis based on her T-score level (< -2.5) and should be treated to decrease her fracture risk.
Note that denosumab (RANKL inhibitor, not provided as an option here) would be ideal in patients with renal impairment as it is not cleared by the kidney.
NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis 2014

28. Case 2
A 42-year-old man falls and sustains a Colles’ fracture of his left wrist. He has no history of sexual dysfunction and does not take any medications.
A DXA scan reveals a Z-score of -2.2 in the spine.

29. Case 2 (cont’d) His initial laboratory studies reveal the following:
Calcium 8.9 mg/dL (normal, )
25-(OH) D 12 ng/mL (normal, )
Urinary calcium 50 mg/24 hours (normal, )
He was treated with vitamin D, and repeat laboratory studies 3 months later revealed the following:
25-(OH) D 32 ng/mL (normal, )
Urinary calcium 80 mg/24 hours (normal, )

30. Question #3 Which of the following tests is most likely to explain these findings?
Serum intact PTH level
Serum testosterone level
Serum TSH level
Serum antibodies for gluten-sensitive enteropathy
Serum protein electrophoresis

31. Answer #3
Which of the following tests is most likely to explain these findings?
A. Serum intact PTH level
B. Serum testosterone level
C. Serum TSH level
D. Serum antibodies for gluten-sensitive enteropathy
In this young man, secondary causes of low bone density must be investigated. He was found to have vitamin D deficiency, but treating this deficiency did not correct his hypocalciuria, which should point to the diagnosis of celiac disease.
The most appropriate test to screen for this condition is serum antibodies for gluten-sensitive enteropathy, such as tissue transglutaminase antibodies.
E. Serum protein electrophoresis

32. Which of the following tests is most likely to explain these findings?
A. Serum intact PTH level
B. Serum testosterone level
C. Serum TSH level
D. Serum antibodies for gluten-sensitive enteropathy
E. Serum protein electrophoresis
The other options listed may be useful in evaluating patients with abnormally low bone mineral density, but these do not test for conditions associated with vitamin D deficiency and do not explain the clinical findings in this scenario.
The patient is not hypercalcemic and is not reported to have signs or symptoms of hypogonadism or thyroid dysfunction.
Hudec SM, Camacho PM. Secondary causes of osteoporosis. Endocr Pract. 2013; 19:

33. Case 3
A 68-year-old postmenopausal Caucasian woman has a DXA scan to test for osteoporosis. She recently sustained a wrist fracture (tripped while walking).
She takes OTC calcium and vitamin D supplements. She has no history of chronic glucocorticoid use.
She does not smoke or drink alcohol excessively. Her mother fractured her hip at age 86.

34. Case 3 (cont’d)
Physical examination reveals mild thoracic kyphosis but is otherwise unremarkable, with no spine tenderness to palpation.
Her bone density test reveals a T-score of -2.1 in the left femoral neck.
Her calculated 10-year risk of a major fracture is 27% and hip fracture is 5.7%.

35. Question #4 Which of the following is the most appropriate next step in her management?
Continue calcium and vitamin D replacement therapy but no additional treatment for her low BMD at this time
Start osteoporosis therapy
Start osteoporosis therapy only if spine imaging reveals a vertebral compression fracture
Repeat DXA scan in 3-5 years since she does not have osteoporosis

36. Answer #4
Which of the following is the most appropriate next step in her management?
A. Continue calcium and vitamin D replacement therapy but no additional treatment for her low BMD at this time
B. Start osteoporosis therapy
This patient is at high risk of fracture based on her FRAX calculation (her 10-yr risk of major fx is >20% and hip fx is >3%).
Therefore, she should be offered treatment for her low bone density even though she does not meet osteoporosis T-score criteria.
C. Start osteoporosis therapy only if spine imaging reveals a vertebral compression fracture
D. Repeat DXA scan in 3-5 years since she does not have osteoporosis
NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis 2014

37. Which of the following is the most appropriate next step in her management?
A. Continue calcium and vitamin D replacement therapy but no additional treatment for her low BMD at this time
This is not adequate since this patient is at high risk for future fracture.
B. Start osteoporosis therapy
C. Start osteoporosis therapy only if spine imaging reveals a vertebral compression fracture
This patient should be offered treatment regardless of whether or not she has a vertebral fracture on imaging.
D. Repeat DXA scan in 3-5 years since she does not have osteoporosis
A DXA scan should be repeated in 1-2 years to assess her response to therapy.
NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis 2014

38. Questions?