Salmon Calcitonin After Spine Fractures?

In my last post, I reviewed some data on the effectiveness of starting Vitamin D supplements after a patient sustains a fracture. The idea was that they might start building better bone and heal their fractures more readily if they boost their D levels. Unfortunately, this was not shown to be true.

Vitamin D improves bone health by facilitating absorption of calcium from the gut. This is a bit indirect and relies on sufficient intake of calcium and good hormonal regulation that directs osteoblasts to incorporate the mineral into bone. Why not work with those hormones directly to try to increase the amount of calcium that is deposited?

Calcitonin is a peptide hormone that has two major effects on calcium levels: it inhibits osteoclast activity that is breaking down bone and releasing calcium from it, and it inhibits calcium reabsorption in the kidneys which causes more to be excreted in the urine.

Perhaps giving calcitonin after sustaining a fracture might improve healing. Many orthopedic surgeons and neurosurgeons swear by this drug. Unfortunately, there are very few randomized, controlled studies of its use for this indication. A meta-analysis was performed that examined both utility and cost-effectiveness that I found interesting.

Here are the factoids:

  • There was some mild evidence that nasal calcitonin was effective in preventing vertebral fractures
    • One paper showed a benefit when giving 200 IU of intranasal salmon calcitonin daily over a 5 year period
    • But a benefit was not shown if 100 or 400 IU were given (this is weird)
    • A marker of bone turnover showed equal reduction in 200 and 400 IU groups (why isn’t this less in the 200 IU group?)
  • Financial analysis showed that it was only marginally cost effective
  • Current retail pricing is about $125 for a month supply
  • Mild side effects like runny nose and nausea are common
  • Intranasal calcitonin has been shown to reduce pain during healing of vertebral fractures

Bottom line: What does all of this mean? First, salmon calcitonin might decrease the number of future vertebral fractures. I say might because only the 200 IU dose in the study showed this effect. I can see where higher doses might be more effective to a point, but having only the middle dose show up as effective is just odd and makes me worry about the study.

The data does seem compelling that taking this product decreases pain during fracture healing. A meta-analysis of this showed that the effect probably only lasts up to a month. 

And finally, from a cost-effectiveness standpoint for avoiding future fractures, this medication is marginal. Luckily, it is relatively cheap at $125 retail and about $25 with insurance in the US. 

Wrapping it all up, intranasal salmon calcitonin might reduce fracture pain for a month and might decrease the likelihood of future vertebral fractures. However, the data are weak enough that cost-effectiveness is borderline. And there are more effective (and cheaper) analgesics available.

The absolute best way to strengthen bones is to exercise, especially engaging in weight-bearing activities. Not only does this strengthen bones, it also increases overall fitness and health. In general, medications are not the way to go to strengthen bones. It took decades for your patient to become osteoporotic. And while these drugs might improve their bone density slowly, a graduated and supervised exercise regimen is probably the best thing you can do for them.

References:

  • Efficacy of calcitonin for treating acute pain associated with osteoporotic vertebral compression fracture: an updated systematic review. CJEM 2020 May;22(3):359-367.
  • A Randomized Trial of Nasal Spray Salmon Calcitonin in Postmenopausal Women with Established Osteoporosis: the Prevent Recurrence of Osteoporotic Fractures Study. PharmacoEconomics, 2001, Vol.19 (5), p.565-575.
  • A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. Bone 2016 Oct;91:122-9.

Giving Vitamin D After Fracture: Helpful Or Not?

The role of Vitamin D in fracture healing is well known. So, of course, trauma professionals have tried to promote Vitamin D supplementation to counteract the effects of osteoporosis. A meta-analysis of of 12 papers on the topic relating to hip and other non-vertebral fractures showed that there was roughly a 25% risk reduction for any non-vertebral fractures in patients taking 700-800 U of Vitamin D supplements daily.

Sounds good, right? So what about taking Vitamin D after a fracture occurs? Seems like it should promote healing, right? A large meta-analysis in an orthopedics journal looked at this very question.

Unfortunately, there was a tremendous variability in the interventions, outcomes, and measures of variance. All the authors could do was summarize individual papers, and a true meta-analysis could not be performed.

Here are the factoids:

  •  81 papers made the cut for final review
  • A whopping 70% of the population with fractures had low Vitamin D levels
  • Vitamin D supplementation in hospital and after discharge did increase serum levels
  • Only one study, a meeting abstract which has still not seen the light of day in a journal, suggested a trend toward less malunions following a single loading dose of Vitamin D

Bottom line: Vitamin D is a great idea for people who are known to have, or are at risk for, osteoporosis and fractures. It definitely toughens up the bones and lowers the risk of fracture. However, the utility of giving it after a fall has not been shown. Of the 81 papers reviewed, none showed a significant impact on fracture healing. The only good thing is that Vitamin D supplements are cheap. Giving them may make us think that we are helping our patient heal, but it’s not. 

What about the use of calcitonin for preventing future fractures? Find that in my next post!

References:  

  • What is the role of vitamin D supplementation in acute fracture patients? A systematic review and meta-analysis of the prevalence of hypovitaminosis D and supplementation efficacy. J Orthopaedic Trauma 2016 Feb;30(2):53-63.
  • Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293(18):2257-2264, 2005.

What Is The Curbside Consult?

Surgeons, I’m sure you’ve had an experience something like this at some point:

You happen to be wandering through the emergency department and one of your Emergency Medicine colleagues approaches you and says, “Hey, I ‘ve got this patient I’m seeing that I just want to run by you…”

How should you deal with this? They want a quick tidbit of information to help them decide what to do with the patient. Can they send them home, or should they “formally” consult you?

It’s important to look at the pros and cons of this practice. First the pros:

  • It’s direct. You’re right there. No phone calls, no paging.
  • It’s quick. Just a quick description  of the problem, and a prompt answer. Then everyone can get on with their business.

But then there are the cons:

  • Situational accuracy. The consultee has not seen the patient, so the information they have been given was filtered through the consulter. Any number of cognitive biases are possible, so the real story may not be exactly as it seems.
  • Interpretation of the recommendation. Other cognitive biases are also possible as the consulter acts on and implements the recommendations of the consulter. Have they really been followed?
  • Lack of documentation. This is the biggest problem with a curbside consult. The consultee may act without documenting the source of the recommendation. Or, they may document that they spoke with Dr. Consultee. In either case, one or the other may be hung out to dry, so to speak.

Consider what happens if there is a complication in the care of that patient. There is no way to really determine what was said during that conversation a week or two years later. It boils down to recollections and may end up as a he said … she said situation. And in the worst case scenario, if such a case were to enter the medicolegal arena, there is no official record that any recommendation was made or followed. It’s a very easy case for the plaintiff’s attorney to prevail.

Those of you who have been following me for some time may be familiar with my Laws of Trauma. Originally, there were ten.

But the curbside consult leads to my new Eleventh Law of Trauma:

Work not documented is work not done

Bottom line: There is no such thing as a curbside consult! The consultee should say, “I’d better take a look at this patient, why don’t you officially consult me?”

In doing this, the consulter gets to use their own clinical and cognitive skills, and thus render a real opinion based on first hand experience. The consultee gets the most accurate recommendations possible, and they are noted in the record so there is no room for misinterpretation. And finally, there is good documentation from both that will stand up in a court of law if needed.

The Second Head CT In Patients Taking DOACs

Direct oral anticoagulant drugs (DOACs) are here to stay. When they were first released, I was very concerned with our inability to reverse them. I feared that we would have a rash of our elders presenting with severe head bleeds that we could do nothing about.

Well, that has not materialized. In fact, it appears that the probability of serious bleeding is more likely with our old reversible workhorse drug, warfarin.

But we are still spooked by DOACs. Nearly every center that has a practice guideline for managing patients with TBI on blood thinners includes a repeat CT scan after a given time interval. This is typically 6, 12, or even 24 hours.

Given the evolving safety profile of DOACs, is this even necessary? The surgical group at the Henry Ford Wyandotte Hospital in Michigan performed a retrospective registry review for their Level III trauma center. They reviewed the data for all adult patients who had suspected or confirmed blunt head trauma (any mechanism), were taking a DOAC, and received at least one CT scan.

Here are the factoids:

  • There were 400 patients with 498 encounters (yes, 15% came back with another TBI)
  • Patients were elderly (mean age 76) and nearly evenly split by sex
  • Fall was the most common mechanism (97%)
  • The first scan was negative in 96% of patients;12% of them did not have a repeat scan
  • Of the 420 patients who had a second scan, 418 were negative (99.5%). The two with positive scans were discharged uneventfully.
  • There were no differences based on specific DOAC, presenting GCS or mechanism

Bottom line: This is a relatively small, single institution study. However, it does appear that the authors have a large population of elderly patients suffering falls. This paper suggests that, indeed, a second scan may not be necessary. This parallels data from my own hospital. But to be on the safe side, keep an eye out for bigger, multi-institutional studies to be sure.

Reference: The utility of a second head CT scan af-ter a negative initial CT scan in head trauma patients on new direct oral anticoagulants (DOACs). Injury, article in press, June 13, 2021.

Are You A TXA Believer, Or TXA Hesitant?

I’ve visited several hundred trauma centers over the past 25 years, and recently I’ve begun to appreciate that there are two camps when it comes to the use of tranexamic acid: the TXA believers and the TXA hesitant.

There have been a number of large studies that seem to suggest a benefit with respect to survival from major hemorrhage, particularly if given soon after injury (CRASH-2, MATTERs). This drug is dirt cheap and has been around a long time, so it has a clearly defined risk profile.

However, many of those hesitant to use it point to the possibility of thromboembolic events that have been sporadically reported. Several years ago, I did my own literature review and found that the number of thrombotic events from TXA was nearly identical to that of transfusing plasma.

JAMA Surgery just published a large systematic review, meta-analysis, and meta-regression that sought to examine the association between thromboembolic events (TE) in patients of any age and involving all medical disciplines, not just trauma.

The anesthesia group at the University Hospital Frankfurt in Germany did a systematic search of the Cochrane Central Register of Controlled Trials, as well as MEDLINE, for randomized controlled trials involving TXA. They covered all published studies through December 2020.

The authors adhered to standard guidelines for con-ducting reviews and meta-analysis (PRISMA). They specifically searched for outcomes involving TEs, such as venous thromboembolism, myocardial infarction or ischemia, limb ischemia, mesenteric thrombosis, and hepatic artery thrombosis. They also tallied the overall mortality, bleeding mortality, and non-bleeding mortality.

Here are the factoids:

• A total of 216 eligible trials were identified that included over 125,000 patients

• Total TEs in the TXA group were 1,020 (2.1%) vs 900 (2.0%) in the control group

• Studies at lowest risk for selection bias showed similar results

Bottom line: The authors concluded that IV TXA, irrespective of the dose, does not increase the risk of thromboembolic events. Period.

Hopefully, this is the final study needed to convince the TXA hesitant that it is safe to administer. They may still argue the efficacy, but at less than $100 per vial it is becoming impossible to ignore.

Reference: Association of Intravenous Tranexamic Acid
With Thromboembolic Events and Mortality A Systematic Review, Meta-analysis, and Meta-regression. JAMA Surgery 156(6):3210884, 2021.

Home of the Trauma Professional's Blog

Do you want to get a daily email every time there’s a new post? See what I’m up to.

Click here to get details and subscribe!

[accua-form fid=”1″]

Subscribe now to the Trauma MedEd Newsletter and get a free copy of my guide, "How To Keep Up With Your Literature"!