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Dear Dr. Endocrine – Can you help?

Jack Wixted Trauma SurgeonJack Wixted, MD, is an Orthopedic Trauma surgeon in the Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center and an Instructor in Orthopedic Surgery at Harvard Medical School.


Ask an orthopedic surgeon about their practice, their operating room, hospital administrators, even about Obamacare – and then stand back. But ask about osteoporosis or bisphosphonates, and most orthopedic surgeons’ eyes will glaze over, a polite smile emerges, and pretty soon you are talking to yourself. Again.
Despite a concerted effort on everyone’s part to get us collectively to “Own the Bone” and despite consistent evidence that osteoporotic medications do in fact work to decrease subsequent fracture rates, treating osteoporosis remains far enough out of our proverbial wheelhouse that most surgeons haven’t even made a down payment on the bone, let alone owning it. Maybe we surgeons are like seventh graders (in more ways than one!) – we really want to talk to that cute boy or girl in homeroom, but we just don’t know enough about how this whole thing works to get started. So we just go on pretending not to notice them … until they break their hip?
With that in mind, I propose a Dear Abby-like forum – everything you wanted to know about bisphosphonates, but couldn’t find out from your best friend in the back seat of the middle school bus.

Dear Dr. Endocrine – I heard that bisphosphonates are good for you. How does that work? Dr. Bone.
Dear Dr. Bone – Bone remodeling is pretty important. If you recall, your skeleton is a large reservoir of calcium (Figure 1). If your calcium levels go up, your thyroid gland will release calcitonin. If your calcium levels go down, your parathyroid gland will release parathyroid hormone (PTH). These actions affect how osteoblasts, which lay down bone, interact with osteoclasts, which resorb bone. PTH, for example, acts on osteoblasts – which in turn stimulate osteoclasts (via Rank Ligand) to work harder – thus releasing more calcium into circulation. Everyone’s bone mineral density peaks at about age thirty, and then declines. This is largely driven by osteoclastic bone resorption. Bisphosphonates are good for you – if you have poor bone density. To the body, these drugs look an awful lot like ionized calcium – and they get incorporated into your skeleton. But the main effect is on the osteoclast – bisphosphonates prevent osteoclasts from resorbing bone and promote osteoclast apoptosis. No osteoclasts – no bone resorption. So the osteoblasts get a competitive advantage, continues to build and add more bone and we see fewer fractures. So remember – practice safe bone! Take a look at this guide online. Clinician’s Guide to the Prevention and Treatment of Osteoporosis, Osteoporosis Int 2014 25(10) 2359–2381, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176573/)

Trauma Rounds Calcium Homeostasis
Figure 1. Calcium Homeostasis.  PTH has a rapid effect (occurring within minutes), whereby it stimulates osteoblasts to pump Ca++ ions out of the fluid surrounding the bone (which has a higher Ca++ concentration) and into the ECF. Over a longer time course, PTH stimulates bone resorption.
Ref:  http://hmsphysiology.pbworks.com/w/page/23885663/PTHCalcitonin%20Control%20of%20Calcium%20Homeostasis

Dear Dr. Endocrine – I get it. But after my patients break something, shouldn’t I stop these medications? ~ Sleepless on Call.
Dear Sleepless – Please practice safe bone. Use a bisphosphonate (Figure 2). Don’t be embarrassed, you can get them at your local CVS or other pharmacy. Kidding aside, bisphosphonates does affect fracture healing. As you recall, endochondral ossification involves indirect healing by formation of cartilage, which is replaced by bone. This requires the cartilage be replaced by bone. Chondroclasts remove (or resorb) the cartilage template and osteoblasts follow behind laying new bone. Bisphosphonates also affect these chondroclasts, dampening their effect. In this sense, remodeling of the callous into bone will certainly take longer. But in animal models, this has been shown to create larger amounts of callous formation. And who doesn’t want that? (Effect of osteoporosis medications on fracture healing, Osteoporosis Int. 2015 Sep 29.) In general, bisphosphonates can safely be continued after fracture.

Trauma Rounds Mechanism of Action of Bisphosphonates
Figure 2. Mechanism of action of bisphosphonates. Bisphosphonates inhibit bone resorption by several different but complementary mechanisms.
Ref:  http://www.medscape.org/viewarticle/520178_5

Dear Dr. Endocrine – But my patients all want to stop taking these drugs. They are afraid for their teeth. I am afraid for their femurs. What’s a gal to do? BoneBroke MeFix
Dear Dr. BoneBroke – Do not despair. Primary care doctors and endocrinologists are there to help. Yes, prolonged use of bisphosphonates can contribute to osteonecrosis of the jaw as well as atypical femur fractures. The risk is clearly related to exposure time to the medications. So yes, after a number of years of bisphosphonate treatment, patients need a drug holiday. Actually, there’s an App for that! The National Osteoporosis Foundation has a nice app for your cell phone that can help you and your patients practice safe bone. In the particular case of atypical femur fractures, in patients who have been on bisphosphonates for a number of years, by all means STOP the medications. Also, check their other femur.

Dear Dr. Endocrine – Are you saying that if my patient has one atypical femur fracture, they can get another? These damn things are hard to treat and seem not to heal well. –TomBradyIs Innocent
Dear Pats Fan – Yes, check the other femur. It’s quite common for both to be involved. After an atypical femur fracture, bisphosphonates need to stop. Published data from Mass General Hospital and the Brigham & Women’s Hospital would suggest that many if not all of these stress fractures progress. So if you find a stress fracture on the contralateral femur, you should discuss the risks and benefits of prophylactic treatment with your patient (Clin Orthop Rel Res 2011 Jul 469(7)). When treating atypical femur fractures surgically, results with nails are generally better than with plates. And yes, atypical femur fractures can take a longer time to heal. A recent randomized control trial indicated average healing times of more than 5 months (J Orthop Trauma 2015 Dec 19). It might even take up to 40 weeks, if you haven’t practiced safe bone. But do not despair, with time, most will heal and secondary procedures are not usually necessary.

Do you have burning…questions? Follow Dr. E at
#IHaveNoIdeaWhatToDoRightNowAndImAnOrthopedicSurgeon #PleaseHelp

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