5 minute read
I From Joint Health: To Bone Health
MOVING
from Joint to Bone HEALTH
The bleeding disorders community is very familiar with and committed to “joint health”. Pharmacokinetic evaluations, EHL versus SHL factor concentrates, novel therapies and MSKUS are now part of the vocabulary. Dialogs about prophylaxis to preserve or improve joint health occur in the HTC, in phone conversations with health care providers, and virtually (and, slowly, in person!!!) between caregivers/ patients/HCP's/MSL's, etc., etc.
But, what about “bone health”? What IS that? Isn’t it just something that older women need to worry about? How does “bone health” affect the bleeding disorders community?
It is true…. women “of a certain age” DO need to be concerned about “bone health” - loosely defined as how strong a person’s bones are - how much calcium exists in the framework of bones over a lifetime. Too little calcium translates into “weak bones”, bones which look less dense (or white) on a plain x-ray (also known as osteopenia) or even bones which are very pale looking with the suggestion of open spaces or holes (osteoporosis). Such women (and I am among their number!) need bone density evaluations (DEXASCANS), and often require calcium supplements, vitamin D supplements, perhaps other medications to enhance the deposition of calcium into the bones or decrease the loss of calcium from bones. Calcium-dense bones maintain their strength and lessen the risk of fracture. We are urged to include weightbearing exercise in our daily routine, as weight bearing helps to maintain the calcium in our bones as well.
Bones are the body’s repository or bank for the minerals, calcium, and phosphorous. Calcium and phosphorous are essential, with functions beyond the formation of bones and teeth. Bones are dynamic. There is a constant balance between the deposition of calcium and phosphorus and the release of these minerals for use by other body tissues.
Osteoblasts are the cells which produce bone tissue. Osteoclasts are the cells in the bone which are responsible for the resorption or breakdown of bone tissue.
Factor VIII
And it turns out that Factor VIII is involved in *Included in this process of this process of regulating the balance in the remodeling bone tissue remodeling of bone tissue.
Deposition of calcium/phosphorus into our bones occurs up until age 27. At that age our bones are as “dense” as they will ever be. From that age on, there is a loss of calcium as it is needed for other purposes, and bones become less dense. Many proteins are involved with bone metabolism: parathyroid hormone, calcitonin, growth hormone, thyroid hormone, sex hormones (estrogen and androgens), vitamin D, glucocorticosteroids produced by the body, and many other recently identified or studied “marker proteins of bone activity”. How they all fit together, and how factor VIII interacts with these is complicated and is only now being pieced together.
Before prophylaxis with factor VIII concentrate, in the era of on-demand therapy (or no therapy), the reality was that hemophiliacs, particularly severes, had low bone mineral density --- even in childhood, with the associated risks of fracture, pain, etc. Makes sense. If a PWH (person with hemophilia) is not active due to frequent bleeds, then the deposition of calcium is compromised. The inflammation induced by a bleed leads to the deterioration of bone and cartilage, further impairing bone density/ strength.
Recent research has demonstrated that Factor VIII itself is involved with the activation of osteoblasts in rabbits—leading to deposition of bone as a secondary effect of the completion of the clotting process with the formation of thrombin. A deficiency of factor VIII leads to less thrombin production (and bleeding!) and therefore less activation of the bone-depositing osteoblasts. Factor VIII deficiency is an independent risk factor for osteoporosis! It is important to note that factor IX deficiency is not associated with increased bone resorption. However, all of this is under investigation. There has been an overall improvement in bone health (density) with the adoption of prophylaxis with factor VIII concentrate. On-demand or episodic infusions do not
result in improved bone health in the long run. This makes sense - consistently replacing the clotting factor that Hemophilia A patients lack results in both the actions of factor VIII in coagulation AND in the bone health balance. But we know that weight-bearing exercise/activity leads to increased calcium deposition in bones, and denser, stronger bones. How much of the documented improvement in bone density in PWHA on prophy can be attributed to the increased mobility and activity that adherence to prophylaxis brings, as the number of joint bleeds decreases in any individual? It’s impossible to say, although, clearly, bone health is the result of many interactions.
We are now entering an era of non-factor therapies. Prophylaxis for both inhibitor and non-inhibitor Hemophilia A patients with emicizumab is a reality. There are other non-factor products under clinical investigation. The question has already been raised: how will bone health be affected if actual factor VIII is not being used? We don’t know. Emicizumab is not factor VIII. As far as it’s known, emicizumab provides the FVIII–like role in coagulation, but may not provide the other functions of factor VIII.
As a community, both treaters and families, we recognize the improvement in joint health and lifestyle experienced by many patients prescribed emicizumab. These patients are walking more, engaging perhaps, in more sports… in other words, improving their bone health/density through activity. (Of course, a healthy diet which includes calcium/vitamin D-rich foods or supplements helps as well!)
This question is already under study. What are other laboratory markers for bone health? Several studies already include collection of blood for evaluating not only the known markers and banking the specimens for evaluation of markers in the future as they are identified. Assessment of joint health using PT evaluations and serial musculoskeletal ultrasound exams is already underway. There will soon be studies which include monitoring of bone density through DEXASCAN imaging.
There will be a lot of information generated, and our knowledge base and changes to the therapeutic approach recommended for our patients will evolve.
Talk to your HTC team to determine how to maximize bone density no matter what prophylactic regimen is prescribed. Currently, relief of pain, improvement in overall joint health, and improvement in lifestyle are accessible goals! Adherence to any available prescribed prophylactic regimen is key!
DEXASCAN
Authored by: Maria Bastos, MD Lawrence P. Cahalin, DPT Fernando F. Corrales-Medina, MD Joanna Davis, MD Kelli A. Fraga, DPT Rachel Leeman, MD Leandro Pisani
