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Why a CBC Holds Great Value When Assessing Osteoporosis-Related Fracture Risk

Ask any doctor what your CBC (Complete Blood Count) lab test can tell him or her about your fracture risk...about breaking a bone from osteoporosis...and you will probably receive a blank stare in return. Doctors are typically focused on looking for infection, anemia, or blood clotting disorders when assessing the indices of a CBC. But bone health?... It's usually not on their radar.

Surprisingly, there is a wealth of information that can be gleaned from a CBC regarding bone quality and the risk of bone fracture. Unfortunately, most doctors don't realize this. Several weeks ago I wrote a blog about CBCs, but thought I would add to it because of the importance of this inexpensive, readily available test.

Within a CBC, there are just shy of 20 indices that measure various quantity and quality aspects of red, white, and platelet cells within your blood. The following is a brief summary of some of the information we can learn from these tests as they pertain to osteoporosis.

Red Blood Cell (RBC):

A low red blood cell count (RBC) may indicate much more than just anemia. When the RBC is even slightly low, it may be from an accumulation of fat cells within the bone marrow. The amount of fat found in bone marrow is unrelated to the amount of subcutaneous fat found in the rest of the body. Excess fat of any kind isn't good, but at least with body fat, we see it and have ways to get rid of it and monitor the loss by using a weighing scale. The problem with bone marrow fat is that, more times than not, it goes unnoticed...a hidden health hazard that can cause a host of problems. And it's really tough to get rid of.

Excess bone marrow fat crowds out the RBC-forming hematopoietic stem cells. With lower amounts of these stem cells the production of RBCs decreases. When RBCs are low, it may be a red flag that the person has less than an optimal number of bone-forming osteoblasts in their bones. This is because fat cells in bone marrow produce a substance (palmitic acid) which is toxic to osteoblasts. With elevated levels of this fatty acid, the number of osteoblasts plummets and bone formation is compromised.

This is one of the reasons that I often order an osteocalcin or P1NP test when I see low RBCs in a patient's lab work. Osteocalcin and P1NP are bone formation markers that give us an indication of how much (or little) bone-building activity is taking place within the inner workings of their bones. The following can help lower the toxic effects of marrow fat and boost osteoblastic activity:

- adequate protein intake

- a diet rich in essential fatty acids

- optimal level of vitamin D (40 to 60 ng/mL)

- supplemental L-carnitine and alpha-ketogluterate

- regular exercise

The adverse effects of having excess fat in bone marrow is like a stone thrown into water...the ripples just keep going. The ripples of marrow fat are especially profound when immersed in a milieu of pro-inflammatory cytokines. These cytokines are the immune system's messenger molecules and in patients with chronic systemic inflammation and high oxidative stress, there is increased production of PPAR- gamma, a protein that stimulates the osteoclasts to break down bone.

After all this negative stuff about bone marrow fat, I wish I could tell you to simply go run around the block a few times...but it doesn't work that way.

Neutrophil/Lymphocyte Ratio (NLR):

As mentioned above, inflammation plays a critical role in bone remodeling and is a major cause of osteoporosis. When the body is healthy and the immune system calm, two of the major forms of white blood cells, the neutrophils and lymphocytes, are in balanced harmony. When there is an infection or chronic inflammation (for example in dysbiosis with a bacterial overload in the gut) the number of neutrophils in the blood can rise causing a change in the neutrophil to lymphocyte ratio (NLR). Neutrophils secrete copious amounts of RANKL, a direct stimulant to osteoclastic bone resorption. (To learn more about gut health and RANKL and the impact they can have on bone please see my book, The Whole Body Approach to Osteoporosis.) Therefore, when we have too many neutrophils in relationship to the number of lymphocytes, we can have increased bone loss.

The number and ratio of lymphocytes in the blood stream can be reduced even further when the bacteria-eating macrophages (another type of white blood cell) come to the bodies defense during bacterial overgrowth. Macrophages release an enzyme that stimulates the liver to produce more calcitriol, the active form of vitamin D. This increase in calcitriol stimulates the immune response, boosting the bacteria-killing capability of macrophages, but also dampening the call for additional immune reinforcements by way of lymphocytes. The result is an elevated NLR. NLRs greater than 2.5 have been linked to low bone mineral density.

And speaking of more ripples... When a patient has issues with dysbiosis, the increased numbers of macrophages in their gut may cause the liver to produce too much active vitamin D. The result is excess calcium absorption (yes, all things in moderation) and an unexplained, abnormal increase in blood calcium levels (hypercalcemia) and high levels of calcium in the urine (hypercalciuria).

Mean Platelet Volume (MPV):

Elevated MPV is an early marker for platelet cell activation seen in low-grade inflammation. It is low-grade chronic systemic inflammation that is the main fuel behind all chronic disease, including osteoporosis.

Red Cell Distribution Width (RDW):

The size of red blood cells becomes more variable with age and the RDW is an indication of this variability. An RDW greater than 14% carries a greater risk for fracture. In fact, by looking at RDW in combination with bone density (DXA) T scores, researchers have found this to be more accurate for predicting hip fractures than using FRAX (an on-line fracture risk assessment tool) with bone density. (Kim, K.M., et al. 2019 ASBMR Ann Meeting Abstracts, #1069)

Hemoglobin (Hgb):

A whopping 73% of the iron stored in the body is located in the hemoglobin (Hgb) of RBCs. Hgb carries the oxygen we need to perform physical exercise and for the brain to function with acuity. That's why when iron and Hgb are low we experience great fatigue and reduced cognitive function. Oxygen is also important for bone growth and with hypoxia (low oxygen) we have diminished bone formation and heightened bone loss, a recipe for osteoporosis.

Low iron/Hgb levels can be from excessive menstruation, poor nutrition or malabsorption, and it doesn't just impact physical performance and cognitive function. Low iron can also have negative effects on the immune system and increase the susceptibility to infections. As I mentioned above, a balanced immune system is key to bone health and when it's out of balance we lose bone.

Iron is also needed for the production of calcitriol, the active form of vitamin D which helps us absorb calcium from the gut, and for the formation of the triple helix structure during bone collagen formation by the osteoblast cells. So yes, we need adequate iron for good bone health but too much is harmful. Excess iron can increase oxidative stress causing bone loss with increased incidence of osteoporosis.

Mean Corpuscular Volume (MCV):

MCV is a measure of the average size of red blood cells. When elevated, it may indicate a deficiency in vitamin B-12 and/or folate. Pernicious anemia is a condition that reduces the absorption of vitamin B-12 and calcium. Vitamin B-12 has a direct influence on osteoblastic bone-building activity. An elevated MCV is a flag to look at homocysteine, a protein metabolite that contributes to chronic systemic inflammation and reduced bone quality.


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