#47 Osteoporosis Part 2: bone markers, fracture risk, and more on calcium and Vitamin D

July 10, 2017 | By Matthew Watto, MD

Solidify your knowledge of osteoporosis and osteopenia in this discussion with Endocrinologists and osteoporosis guideline authors, Dr. Rachel Pessah-Pollack, and Dr. Dan Hurley from the American Association of Clinical Endocrinologists (AACE). Learn when to start therapy after an acute hip fracture, how to use bone turnover markers to assess fracture risk, more on how to dose calcium and vitamin D, and finally, we discuss the new American College of Physicians (ACP) guidelines and how they differ from the AACE guidelines on osteoporosis.

For a more basic talk on osteoporosis check out episode #18 w/Dr. Pauline Camacho.

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Case:  66 yo F with new diagnosis of postmenopausal osteoporosis without a current fracture.

Clinical Pearls:

1. Definition: Osteoporosis is low “bone quality” that puts one at risk for fracture. Should meet 1 of 4 criteria: T-score -2.5 or below in the lumbar spine, femoral neck, total, and/or 33% (one-third) radius; Low-trauma spine or hip fracture (regardless of bone density); Osteopenia or low bone mass (T-score between -1 and -2.5) with a fragility fracture of proximal humerus, pelvis, or possibly distal forearm; Low bone mass or osteopenia and high FRAX® fracture probability based on country-specific thresholds (See table 5 in AACE guidelines).
2. Fractures: Most occur in patients with osteopenia! Thus, calculate a FRAX score.
3. FRAX score: 10 year risk of fracture in patients with osteopenia. FRAX can be calculated even without a known bone mineral density (BMD). If risk for major osteoporotic fracture above 20% or risk of hip fracture above 3% then treatment recommended.
4. Secondary workup for osteoporosis: Check calcium, 25-OH Vitamin D, parathyroid hormone. Consider testing for celiac disease, or multiple myeloma if clinically suggested.
5. 25-OH Vitamin D: Assay varies by about +/- 10%. Thus recommendation for level 30-50.
6. Calcium supplements: Give calcium carbonate with meals to improve absorption. Calcium citrate can be taken with or w/o food.
7. Bone turnover markers: N-telopeptide (urine), C-telopeptide (blood), and bone specific alkaline phosphatase are markers of bone turnover.  Possible uses: monitor compliance w/therapy, determine when to end drug holiday (i.e. resume therapy if elevated).
8. C-telopeptide (CTX): Blood marker (measures collagen in blood) that indicates bone turnover. Drop by 40% on therapy suggests benefit. Can potentially be used to monitor compliance, or to determine when resume therapy after a drug holiday (expert opinion).
9. Alkaline phosphatase: Predominantly from bone and liver. Less so from intestine. Often due to Vitamin D deficiency and with subsequent increased bone turnover. Consider checking fractionated isoenzymes, or a bone specific alkaline phosphatase to determine source. This can help diagnose Paget’s disease.
10. Antiresorptive agents for bone: oral bisphosphonates (alendronate, risedronate), IV bisphosphonate (zoledronic acid), subcutaneous denosumab.
11. Anabolic agents for bone: Teriparatide and abaloparatide are both available. Once daily dosing causes bone formation with positive changes in microarchitecture. In trials, continuous or multiple daily doses caused bone loss. Alkaline phosphatase and telopeptides become elevated on these agents.
12. Anabolic window: Early on therapy w/anabolic agents bone formation >> bone resorption → improved bone quality. This effect cannot be detected on BMD (DXA) testing.
13. Aromatase inhibitors: Block conversion of androgens into estrogen → Low estradiol → enhanced bone loss → high fracture risk. Need baseline and follow up BMD testing.
14. When to start therapy after an acute fracture: First, ensure vitamin D level at goal of 30-50 (may take up to 12 weeks). Then, ensure adequate calcium and vitamin D intake for maintenance. Initiate a bisphosphonate 2 to 12 weeks after fracture (expert opinion), but not before vitamin D at goal. There is no data to suggest impaired fracture healing even if patient was already on bisphosphonate at time of fracture.

Goal: Listeners will review the basics of treating osteoporosis and utilize advanced monitoring techniques to lower fracture risk.

Learning objectives:
By the end of this podcast listeners will:

1. Define osteoporosis
2. Recall utility of the FRAX score with or w/o known bone density
3. Perform a secondary evaluation for causes of osteoporosis
4. Utilize bone turnover markers in management of osteoporosis
5. Recall how aromatase inhibitors affect bone density
6. Decide when to start antiresorptive therapy after an acute fracture
7. Choose the appropriate dose and frequency of calcium and vitamin D
8. Recall the differences between the AACE and ACP guidelines for osteoporosis

Time Stamps
00:00 Intro
03:00 Picks of the week
07:31 Guest and topic intro
10:25 Rapid fire questions
14:45 Clinical Case and defining osteoporosis
17:00 FRAX score
20:35 Secondary evaluation for cause of bone loss
20:54 Bone turnover markers (telopeptides)
23:17 Alkaline phosphatase
26:30 Calcium and Vit D
29:35 Recap of teaching points so far
31:25 Antiresorptive versus anabolic therapy
32:40 Aromatase inhibitors increase fracture risk
34:28 When to start therapy after fracture
35:44 Mechanism of action recombinant PTH
41:38 Vitamin D assay and dosing
46:53 Calcium intake, and formulations
49:45 Take home points
50:54 Recap and discussion of AACE vs ACP guidelines by The Curbsiders
59:42 Outro

Links from the show:

1. Moonlight (film) on Amazon
2. Room (film) on Amazon
3. Startup School (podcast) by Seth Godin on iTunes
4. Linchpin (book) by Seth Godin
5. Purple Cow: Transform your business by being remarkable (book) by Seth Godin
6. AMPLIFY Trial: Apixaban for acute venous thromboembolism NEJM 2013
7. AACE response to ACP guidelines 2017
8. AACE Osteoporosis Guidelines 2016
9. ACP Osteoporosis Guidelines 2017
10. FLEX study for optimal duration of treatment JAMA 2006
11. Aromatase inhibitors and breast cancer NEJM 2016
12. AACE Osteoporosis treatment algorithm (app) from iTunes
13. Calcium content of foods (handout) from University of Chicago