Did you know that surgery can trigger a drop in phosphate levels in your blood, and it can happen to anyone, not just XLHers? It’s seen in high percentages of patients after general surgery, liver surgery, and cardiac surgery. See “Hypophosphatemia following open heart surgery: incidence and consequences” in the European Journal of Cardiac Surgery (2004). That article is talking about the general population, not XLHers, and discusses a number of possible causes for the drop in blood phosphate levels, none of which are FGF23-related.
So the hypophosphatemia can happen to any patient, but dealing with it is trickier for us. Normally, when a surgical patient develops low phosphorus, the surgeon will order phosphorus supplementation, and that takes care of the problem. But supplementation is complicated for us. The standard protocol for post-surgical hypophosphatemia says nothing about active vitamin D, and we all know, I hope, that we should never take “unopposed phosphorus” (phos supplements without active vitamin D), or else we can end up in a feedback loop where our blood phos levels rise and our parathyroids think it’s a problem and order more phosphate-wasting, so, paradoxically, we can end up with less phos in our blood than we started out with! Plus, adding phosphate supplements to a patient on burosumab can lead to too-high levels of phosphorus and potentially nephrocalcinosis.
I’ve been thinking about this issue since my cardiac surgery, when I did develop fairly severe hypophosphatemia and was prescribed a phosphate supplement (which I declined). As always with medical issues, the devil is in the details, and everyone’s situation is a little different, so I’m not suggesting anyone follow what I did. I’m not sure anyone knows the “right” answer to treating surgery-induced hypophospatemia in XLHers. It may well depend on what treatment the person was on prior to surgery and how severe the hypophosphatemia is, as well as other factors I’m not familiar with.
At the time of my surgery, I was on burosumab, which blocks FGF23 and allows my metabolism, at least in theory, to act like a non-XLHer’s. But we don’t really know what adding phos supplements on top of the reduced FGF23 would do. My post-surgical hypophosphatemia wasn’t too bad, just a little below what I lived with for the first sixty years of my life, so I chose to grit my teeth and bear with the fatigue and bone pain instead of risking the supplements. I might have decided differently if instead of burosumab, I’d been on phos supplements and active vitamin D prior to surgery, in which case a single phos pill wouldn’t have made much difference one way or another. Our metabolisms laugh at a single phos pill!
I’m confident my surgically-caused hypophosphatemia is just a temporary thing and will continue to improve with time, but my hospital experience made me aware of this gap in our understanding about what to do with a surgical patient who is on burosumab but develops hypophosphatemia while in the hospital.
There appears to be a gap in both the research on this issue and pharmacies’ warning system. The Crysvita (commercial name for burosumab) label states that it is “contraindicated: In concomitant use with oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia [which can cause nephrocalcinosis].”
Basically, the label is saying, “don’t give burosumab to patients who are taking phosphate supplements and active vitamin D.” I think, logically, the reverse would be true too: “don’t give phosphate supplements to patients who are on burosumab.” But there doesn’t seem to be any such warning for pharmacists who are filling phosphate prescriptions.
It’s complicated, because burosumab is distributed through specialty pharmacies, and I’m sure those pharmacists know (or have a warning in their computer systems) to check the patient’s list of current medications to make sure it doesn’t include phos and active vitamin D before they fill the prescription. But regular pharmacies don’t distribute burosumab, so the pharmacists are unlikely to have even heard of it, and apparently (based on my experience and at least one other patient’s similar experience) there’s no flag in regular pharmacies’ computer systems for the situation where a patient is already on burosumab and the pharmacist is being asked to fill a prescription for phos.
I’m not even sure what the flag should say. I’m not a doctor, and as far as I know, there isn’t any research into what’s the best way to treat surgically-caused hypophosphatemia in patients on burosumab. So, maybe it’s okay to take a single phosphate supplement? Or up to a certain number of pills? Or it’s better not to? And if we do take the supplement, should we also take calcitriol? Or not? I don’t know, and I don’t think anyone knows for sure. Which means, I believe, that it should be left to an expert clinician in consultation with the patient, not a health care provider who’s never head of XLH before.
One solution, until there’s a consensus on appropriate treatment for post-surgical hypophosphatemia in patients on burosumab, would be to create a flag that simply requires pharmacists to check with the patient’s XLH (or TIO) specialist before filling a prescription for phos. Obviously, once there’s a consensus on the standard of care in this situation, then the flag can be replaced with that advice, but until then, we need a way for pharmacists outside the specialty pharmacies to be alerted to the potential problem with mixing phosphate supplements with burosumab.
As noted, I can’t tell you what to do in terms of treatment, and I would never try to give you medical advice. I do have three suggestions for advocating for yourself if you anticipate undergoing surgery. First, talk to your endocrinologist (or other specialist treating your XLH) about what should be done if your phosphate levels drop while you’re in the hospital/rehab. Second, once you have a treatment plan from your specialist, prepare to advocate for that treatment. Write out a script or practice what you’ll say to a nurse (or clinician) if offered a treatment that’s inconsistent with what your specialist recommends. It sometimes helps to present your self-advocacy in terms of just wanting to follow your specialist’s advice: “I’m sorry, but my rare disorder specialist has told me [whatever the advice is], so I can’t [do whatever the surgical health care provider is advising].”
Finally, if you don’t think you can stand up to a health care provider (hard to do in the best of circumstances and even harder if you’re in pain and overwhelmed by the hospital experience), see if a family member who understands the situation is willing and able to do it for you. If that’s not an option, some hospitals have patient advocates on staff, and you can reach out to them before the surgery with your concerns. Another option is to ask your specialist to write a letter to your surgeon in advance, advising what to do (or not do) if the phosphorus levels go below a certain number, and then you (or your advocate) just has to make sure the letter isn’t overlooked.
I know a lot about XLH, but I was so focused on how my rare disorder might affect my healing (trying to schedule my surgery around my burosumab doses so as to be at peak effectiveness right after the surgery) that I never realized there was a common risk of hypophosphatemia after surgery that non-XLHers also experience and that I needed to prepare for! I hope that sharing my experience will help other XLHers to be better prepared than I was.
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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