Hypocellular bone marrow. Can anyone tell me more?

[newlandvale]

I was diagnosed with B12 deficiency ("low serum B12") over 15 years ago when debilitating exhaustion was putting my job at risk. Doctors assumed diet related because I was usually vegan at home but still ate meat and fish two or three times a week. I am diary intolerant with eczema (but crave custard and yoghurt, preferably together!!).

I was put on 12-weekly injections, without further testing or loading doses, after tablets did nothing. I think the doctor may have thought I was non-compliant re tablets as she read the riot act re the seriousness of B12 deficiency. Those were the days ... real doctors!

I was diagnosed with me/cfs , an immune system related neurological disease, the development of which, I believe, may be caused by inadequate B12. Other neurological diseases seem to be related to B12 deficiency - cause or effect? - it seems the jury is still out.

Five years later, job lost, some tingling and numbness had set in, plus chest pain with no explanation. But most worrying my bowel, which had slowed down, then stopped working for 5 days . Raised MCV 103, then 105 on retest. Eventially persuaded doctor to increase B12 injections to 8-weekly. Fortunately, I now had access to Dr Google.

I have had many different B12-related testing since - bloods, gut, nerves - all blank. I do check.

Fast forward another 5 years, different surgery and county. Doctor decided B12 bloods too high and cut back to 12-weekly but really wanted to stop them altogether. New symptoms appeared - horrendous itching and restless legs. Saw NHS neurologist who quoted NICE Guidelines for itching to GP but no increase in B12 injections. This included testing for MGUS (pre-myeloma).

Positive for MGUS and tested anually. It's more common with pernicious anaemia. Used it to insist on a bone marrow biopsy in the hope it would shed some light on B12 deficiency. By now was self injecting - included loading doses then twice weekly. Stopped injecting when haematology appointment came through. Blood tests clear on the day of appointment but a month later biopsy showed moderately hypOcellular (not hypERcellular) red cells.

Haematologist only wanted to look at myeloma (clear) but I argued by series of letters that the blood tests were showing the results of blood cells made when self-injecting, whilst the bone marrow was showing result of my stopping injections. Peeved haematologist, backed into a corner, gave doctors permission to inject 6-weekly!! So generous ...

Not enough, still self-injecting but would like it made official. Different GP (and new NICE Guidelines). Now have appointment with another haematologist (not holding breath - breathlessness another symptom!) - to discuss bone marrow biopsy done 2 years ago.

Any scientists out there who can tell me more about moderately hypOcellular bone marrow red cells. Since having this test I am now developing bleeds - into skin, eye and now gums. Platelets were always borderline 150,000 when not clumped but now dropped to 130,000.

Sorry to bore everyone but I hoped to supply all info in one go. So if anyone is still awake🥱🤣hope someone can help!🙏

Thank you

[palmier]

I don't know anything about the hypocellular bone marrow, but do you get enough iodine if you're avoiding dairy? Milk is an important source of iodine. Eating fish a few times a week may not be enough.

[newlandvale in reply to palmier]

Thank you palmier. I don't know anything about Iodine but will check it out.

[MarvelDC]

Hi Newlandvale, sounds like you’ve been on quite a journey like most of us, it sounds like your covered from a B12 point of view since you’ve been injecting for quite a while…. So personally I’d say this is related to something else.

All the symptoms you describe could be related to a few different things, so I suggest you get all the main ones tested first which are ferritin, b12, folate, vit D, thyroid and FBC.

Personally I would say your symptoms sound like an iron deficiency, for this you would need an iron panel done, alot of people who are low in b12 can also be low in iron, and when we start b12 treatment it can cause iron to drop, since b12 can’t do its job without the assistance of many things including iron, doctors idea of normal can be a ferritin as low as 10ug, which is ridiculously low, a ferritin level lower than 70ug can start to cause symptoms, so please look into this, I’ve been going through the same thing for about a year, my doctors said my iron was normal, but it was to low all along with a ferritin of 29ug, I’m self treating now

[newlandvale in reply to MarvelDC]

Hi MarvelDC. My bloods always come back very normal - ferritin 100ug on the last test. The only puzzle is vitamin D - always borderline low in middle of summer. Outside all the time and can't tolerate sun screen with eczema. Need to supplement to keep it respectable. MCV usually 98 and MCH just above range despite injecting.

[MarvelDC in reply to newlandvale]

Ow right ok, well from what I’ve read most deficiencies can cause similar symptoms, so it might be an idea to work on increasing your vitamin D to the top of the range to see if that helps, your eczema might interfere with you absorbing vitamin D since the hormone is created in the skin

[newlandvale in reply to MarvelDC]

Yes, that may explain it now you mention it. Skin is rather dry and looks aged!☹️☹️

[PlatypusProfit8077]

All the stories are epic sagas, aren’t they? You’ve done well fighting for yourself

I’m interested in your MGUS and PA link - do you have any research/papers backing that up? My Mum has MGUS, lupus and a few other things but not PA. I didn’t know there could be a link

[newlandvale in reply to PlatypusProfit8077]

macmillan.org.uk/cancer-inf...

Don't know how to do a link so hopefully above helpful. Have also seen it in research papers somewhere. Will get back if found

[newlandvale in reply to newlandvale]

Also

aacrjournals.org/cebp/artic...

[PlatypusProfit8077 in reply to newlandvale]

Thank you, that’s so interesting! Our bodies are so complex and infuriating and fascinating. I’ll add this to my notes (I’m getting quite a dossier)

[Cherylclaire Forum Support]

I have just Googled MGUS as you had positive test and I am not familiar with this. MacMillan's explanation would be worth reading as it does make a link between pernicious anaemia (also lupus) and MGUS.

[By the way, you have not bored anyone. You have struggled to get adequate treatment, you were experiencing increase in symptoms and made sensible requests for answers. Sound familiar to anyone else here ? This is why we (thankfully) have this forum.]

We have got a few scientists here - sorry I'm not one of them.

[Cherylclaire Forum Support]

FlipperTD - scientist who may be able to help with this !

[newlandvale in reply to Cherylclaire]

Yes, I'm hoping some of the scientists/medics will see this. Maybe shouldn't have posted in this lovely weather when it may not be seen!😆

[Cherylclaire Forum Support in reply to newlandvale]

FlipperTD will get this now. I think others might not reply if, like me, they are unfamiliar with MGUS and so feel unable to help you.

The fact that MacMillan's have acknowledged a link (in print) between PA and MGUS is or could prove useful.

[charks]

What you're going through sounds terrible. My gut feeling is that it is all B12 related. Vitamin B12 deficiency is a well recognised cause of bone marrow failure.

I think you should increase the frequency of your injections and see what happens. It can't hurt. And good luck with getting your SI made official.

P.S. Custard made with oat milk is delicious.

[newlandvale in reply to charks]

Hi Charks. My gut feeling also. Do you know any research papers that show link between B12 deficiency and bone marrow failure that I can wave at haematologist if he disagrees?

I think the cravings for custard and yoghurt is related to B12 deficiency, as the cravings were always worse when in need, ie before I started self injecting!

[PlatypusProfit8077 in reply to newlandvale]

Wouldn’t the bone marrow failure have to do with the anaemic side of PA? Because of the changes to the RBC’s (ie becoming large and irregularly shaped), this impacts their ability in all applications (ie oxygen transport and bone marrow production)

[Jillymo in reply to newlandvale]

This artical might be worth casting an eye over............

ncbi.nlm.nih.gov/pmc/articl....

[newlandvale in reply to Jillymo]

Thank you Jillymo. I will have a look at this and other links others have posted

[mickeymouse42 in reply to newlandvale]

I've had bone marrow oedema syndrome for the past 20 years which has led to osteonecrosis of both knees and joints. The bone marrow swells and leads to subchondral fractures in the joint which if left undiagnosed will result in osteonecrosis.Vitamin D deficiency and deficiency of B12 are symptoms of the disease.

The disease was first observed in pregnant women by Curtis and Kincaid in 1959 and called transient osteoporosis, a misnoma later corrected when MRI scanners identified that it was bone marrow swelling that's the issue.

In my case the underlying issue is bile acid malabsorption BAM which is associated with Vitamin D and B12 deficiency.

The underlying cause of BAM is considered to be deficiency of the FGF19 hormone. FGF19 deficiency is also observed in pregnant women.

The main researcher looking at BAM and FGF19 is Professor Julian Walters at Imperial College. He's a gastroenterologist mainly looking at BAM treatments rather than the effects of BAM on the absorption of Vitamins.

I don't think much of this is understood and the research is split across disciplines (gastroenterologists rheumatologists and haematologists) that makes it hard to decipher.

I asked some questions about the link between bone marrow problems and B12 about 3 years ago before I discovered I had BAM:

healthunlocked.com/pasoc/po...

Have you had MRI scans or histology examinations of your bone marrow?

[newlandvale in reply to mickeymouse42]

This information looks very significant. In 2019 I had x-rays of hips and knee because of pain but dismissed because only mild arthritis found. I insisted on MRI because I thought it must be a soft tissue problem. MRI found Bone Marrow Oedema. When queried with doctors and consultants, I was always told the oedema was caused by arthritis. Not logical in my case as arthritis was mild, but no one could explain the logic!! Recently a physio diagnosed severe arthritis, was surprised to find 2019 x-ray found only mild arthritis, ordered new x-rays which showed now moderate arthritis. Everyone in NHS just tells me it's my pain tolerance thats at fault!!

You say In my case the underlying issue is bile acid malabsorption BAM which is associated with Vitamin D and B12 deficiency. Which specialty did you see for this diagnosis and do you mind me asking what symptoms led to a diagnosis of BAM

Thank you for your help in this. I was reading your post from 3 years ago just last night. It appeared in the related posts section. I have a lot of googling to do before next appointment☹️☹️

[mickeymouse42 in reply to newlandvale]

It's just guess work to suggest that bone marrow oedema syndrome is caused by arthritis. The literature doesn't support this view at all.

If you have had bone marrow oedema syndrome, you need to see a bone metabolic consultant (a sub division of Rheumatology). The key treatment for bone marrow oedema syndrome is to ensure that you do not put pressure on the joint. If you've got it in your knee or ankle, weight bear on the other knee or ankle and use a crutch or walking stick on the other side. If you've got it in your hip, it's almost impossible to remove pressure on your hip (going from a supine position to sitting up to standup up puts pressure on the hip).

People try to treat the disease with osteoporosis drugs (bisphosphanates like zolendronic acid) but theres uncertainty here. Bone marrow oedema syndrome is a physical disease where swelling causes fractures. The bone metabolic life cycle (osteoclasts and osteoblasts) operates at a cellular level. Bone marrow oedema syndrome will eventually cause failure of the bone metabolic system but at a much later stage through a direct physical route.

Bile acid malabsorption is the speciality of gastroenterology. You would only get a referral if you have bowel or stomach symptoms. GPs cannot diagnose BAM; in the UK BAM diagnosis is done via a SehCAT scan where you swallow a radio labelled bile acid capsule, have a 5 minute CT scan and then a follow up scan to see how much bile acid is retained. In America they use a 7aC4 blood test to diagnose BAM but that's not available in the UK. It's estimated that 1 in 100 people have BAM; most people who have IBS probably have BAM; IBS is a diagnosis that should only be given when all the alternatives have been explored.

For a GP the tell tale symptoms of BAM are low B12, elevated triglycerides levels associated with hepatic steatosis (fatty liver disease) which is detected by ultrasound and not by liver function tests.

[newlandvale in reply to mickeymouse42]

The BAM doesn't sound like me, however the bone marrow oedema syndrome is a maybe. Caused by whatever B12 deficiency I have rather than BAM? Thank you for explaining this to me so I can now suggest a referal to a bone metabolic consultant re MRI, in addition to haematologist for bone marrow biopsy findings.

[charks in reply to newlandvale]

How about this article

ncbi.nlm.nih.gov/pmc/articl...

[newlandvale]

Thank you everyone for your responses and suggested links. Amazing that I get more useful information on one healthunlocked chat, than all the NHS professional "experts!! I have seen over the years.

Best wishes to you all❤️