Osteoporosis and Bone Health

(This is a two part series in Osteoporosis. Part 1 is covering background information and Part 2 will cover diet, lifestyle, nutrition, and therapeutic options)

Osteoporosis is a disease that is characterized by low bone mass with bone architecture disruption and bone fragility, resulting in an increased risk of fracture, particularly at the spine, hip, wrist, humerus, and pelvis . Osteoporotic fractures usually occur via a fall from a standing height or less. If you have lived long enough on this planet, you are well aware what an osteoporotic fracture can do to impact the quality of life and what it can do to contribute to morbidity. It is really hard for me to write this because I don't like to be "doom and gloom" type of person researchers state that 21% to 30% of patients who experience a hip fracture die within 1 year (Schnell, 2010). This is really sad as perhaps with more information this could be preventable.

Osteoporosis (and low bone density is extremely common . In 2010, it was estimated that 10.2 million older adults had osteoporosis. By 2020, approximately 12.3 million individuals in the United States older than 50 years were predicted to have osteoporosis. The overall low bone mass prevalence in 2010 was 43.9%, from which we estimated that 43.4 million older adults had low bone mass. (Wright, 2014).

A diagnosis of Osteoporosis is made from World Health Organization (WHO) guidelines made in 1994 . The WHO established a classification of bone mass density (BMD) according to the standard deviation (SD) difference between a patient's BMD and that of a young-adult reference population. This value is expressed as a "T-score" which is assessed by the Dual-energy X-ray absorptiometry (DEXA-scan) . A T-score that is equal to or less than -2.5 is consistent with a diagnosis of osteoporosis, a T-score between -1.0 and -2.5 is classified as low bone mass (osteopenia), and a T-score of -1.0 or higher is normal.

Currently the United States Preventative Task Force recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in women 65 years and older. The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in postmenopausal women younger than 65 years at increased risk of osteoporosis, as determined by a formal clinical risk assessment tool. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.

The assessment of Osteoporosis risk generally includes a fracture risk score. The Fracture Risk Assessment Tool (FRAX) . estimates the 10-year probability of hip fracture and major osteoporotic fracture for an untreated patient (40 to 90 years of age) using femoral neck BMD (g/cm2), when available, and known risk factors for fracture.

These factors that way into risk of fracture include:

  • Advancing age

  • Previous fracture

  • Glucocorticoid therapy

  • Parental history of hip fracture

  • Low body weight

  • Current cigarette smoking

  • Excessive alcohol consumption (3 or more units per day)

  • Rheumatoid arthritis

  • Secondary osteoporosis (eg, hypogonadism or premature menopause, malabsorption, chronic liver disease, inflammatory bowel disease)

Of note, and not on this list is the risk of long term use of proton pump inhibitors as they decrease absorption of Vitamin B12, Calcium , Iron, and Magnesium. (Ito, 2010) What constitutes "long-term" is not understood, however, 5 years or more of use should be questioned as a risk factor of bone density concerns in this author's opinion . Long term-use complications may be preventable with measurement of nutrient deficiencies and repletion.

In a lot of ways the name of the game is to prevent fracture. And, then way to prevent fracture is to reduce fall risk and reduce any of these secondary risk factors if and when possible.

It is fascinating to understand how bones are modeled and remodeled as it gives a clearer sense of why we choose some of the lifestyle and therapeutic interventions to preserve bone.

One thing that jumps out to me is that like many chronic diseases bone density concern can be considered a chronic inflammatory disorder. We go into this below.

Bones 101

Our bones are made of two main types of bone matrix trabecular bone and cortical bone.

Trabecular bone (also called cancellous bone) is a light, porous, spongy bone. It lies on the inner aspects of bone in contrast to our core bone called Cortical bone”.

Think of an M&M. The outer shell of the M&M is like the cortical bone and the inner M&M stuff is the trabecular bone. How Naturopathic of me! Importantly, trabecular bone is the site where calcium ions are exchanged (added or removed from bone) (Pizzorno, 2010) Trabecular bone is dense with blood vessels.

Bone mass is made mostly of hydroxyapatite (a complex of minerals) and collagen which is mainly Type I collagen.

Hydroxyapatite is a naturally occurring mineral form of calcium . Up to 50% of the volume of bone is made up of Hydroxyapatite.

Bone flexibility is provided by Type 1 collagen (a common form of connective tissue ). What makes the collagen flexible is the unique structure of the molecules that compose it. Collagen is made of a triple-helical structure made up of and abundance of three amino acids: glycine, proline, and hydroxyproline.

Type I Collagen fibers have tremendous tensile strength. Gram for gram type I Collagen is stronger than steel. (Lodish, 2000).

Bone Physiology Components

Osteoblasts: Osteoblasts are bone matrix producing cells that differentiate from mesenchymal stem cells and are transcribed by the gene Runx2 (runt-related transcription factor 2, aka Osf2 and Cbfa1). Runx2 belongs to the RUnt family of transcription factors, in which the Runt domain binds DNA at response elements called OSE2. Runx2/Osf2/Cbfa1 knockout mice have no bones.

Osteoclasts: Are bone matrix reabsorption cells that are a normal part of the bone remodeling process but when excessively active they can lead to bone degenerative disorders .

In mouse models, chronic inflammation from experimental Rheumatoid arthritis (RA) generating cells such as Th17 cells, B cells,macrophages, neutrophils, mast cells and fibroblast-like synoviocytes leads to a plethora of pro-inflammatory cytokines and RANKL (see below), which are primarily responsible for Osteoclast activation. This points out a key link between inflammation and osteoporosis. (Wu, Adamopoulos.2017)

Hydroxyapatite . A naturally occurring mineral form of calcium Up to 50% of the volume of bone is made up of Hydroxyapatite. Is available in supplement forms.

Osteoprogenitor cells: (OPG) give rise to osteoblasts and osteoclasts.They have no specific markers but are highly proliferative/committed bone cells. Osteoprogenitor cells are located in the marrow space and express parathyroid hormone (PTH) receptors. They have the potential to become osteoblasts or osteocytes.

Osteoid: is a tissue type in the bone that is like cartilage and is flooded with calcium.

Osteocyte: Is a cell that is a fusion of osteoid . It makes Type 1 collagen.

Parathyroid Hormone (PTH). Released by the parathyroid gland to stimulate bone resorption activity for physiological needs. Hyperparathyroidism is a disorder with abnormally high parathyroid secretion leading to excessive calcium reabsorption from bne. PTH is regulated by magnesium (Pizzorno, 2011). Very low levels of magnesium can stimulate PTH secretion. (Vetter, 2002)

Calcitonin : a hormone that suppresses osteoclast activity when blood calcium levels are too high. Regulated by magnesium (Pizzorno, 2011)

Osteocalcin : is a hormone released by osteoblasts that is a signal of bone remodeling process. When carboxylated by Vitamin K2 then calcium is moved into the bone to help with remodeling.

Carboxylated osteocalcin. In order for calcium to bind to bone it requires K2 to carboxylate osteocalcin. So if there is adequate K2 , then osteocalcin gets carboxylated and calcium can improve bone density. The form of K2 that is best for this action is a debatable topic that we will discuss in part 2.

Undercarboxylated osteocalcin (ucOCN). The ratio of undercarboxylated osteocalcin

to total osteocalcin would be ideal to assess the vitamin K status of bone. Undercarboxylated osteocalcin reduces calcium's ability to mineralize bone and points to a Vitamin K deficiency.

Vitamin K2: Vitamin K2 refers to a collection of compounds known as menaquinones that

are individually designated menaquinone-n, abbreviated MK-n, where n is a number between 4

and 13. MK-4 is found primarily in animal products (eggs, cheese,meat) and MK-7 through MK-13 are found primarily in fermented foods (such as sauerkraut and natto/fermented soy).

Vitamin K2 is required for γ-glutamyl carboxylation of osteocalcin, which is secreted by osteoblasts and odontoblasts. (Stankowiak-kulpa, Hanna). It stimulates osteocalcin secretion by osteoblasts so calcium is deposited into bone. It stimulates Osteoprotegerin activity which regulates osteoclastic activity by buffering RANKL. Vitamin K deficiencies in the bone can be predicted by measuring levels of undercarboxylated osteocalcin.

Vitamin D3: helps with the production of Osteocalcin. Vitamin D supplementation may create more K2-dependent proteins to direct calcium into the bones. (van Ballegooijen, 2017)

Vitamin A: At this time of this article the precise role/balance of Vitamin A is not known by this author. It appears it does play a key role in osteoblast and osteoclast activity.

TGF-beta (Tissue Growth Factor-beta). Is a promoter of osteoclast activity that seems to be over-expressed by osteoblasts in post-menopausal osteoporosis patients.(Erlebacher, 1998)

RANKL: (stands for: receptor activator of NF-κB ligand ). is a protein that in humans is encoded by the TNFSF11 gene. RANKL has been identified to affect the immune system and control bone regeneration and remodeling.

RANKL/RANK signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover. Rankl activates pro-inflammatory NF-kappa beta which enters the cell and stimulates osteoclast activity

RANKL’s excessive osteoclastic activity is kept in check by Osteoprotegerin (OPG). It acts as decoy for RANKL, preventing overactivity. (Pizzorno, 2011).

OPG. (osteoprotegerin). A cytokine/immune cell that is released by osteoblasts that inhibits bone reabsorption. (Hall & Guyton, 2011)

It inhibits osteoprotegerin ligand (OPGL) from binding thus preventing bone reabsorption.

OPGL is released by osteoblasts in response to parathyroid hormone signaling.

Highly regulated by estrogen/estradiol as estrogen upregulates OPG expression in Osteoblasts. OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK.

Vitamin K1 and Vitamin K2 and the Isoflavone Genistein all increase OPG activity.

source: Davinci Laboratories.

Diagnosis and Assessment of Osteoporosis and bone disorders

As mentioned the Dexa scan is usually used to assess for bone density measurement. Some providers are also using N-telopeptide (NtX) testing to assess for bone turnover activity.

Rarely we will see bone density issues developing earlier in life (ie in the 30's-40's). If this is occurring secondary tests for bone density factors should be considered these tests would include but not limited to:

  • Complete blood count (CBC) with differential (screens for immune disorder)

  • Blood chemistry (glucose,calcium, phosphorus, magnesium, and renal function). Screens metabolic and nutrient dysfunction.

  • Liver function tests (LFT). Screens for metabolic, immune, and nutrient dysfunction.

  • Thyroid stimulating hormone (TSH), Free T4, Free T3 .( Screens for metabolic dysfunction)

  • 1,25-hydroxy vitamin D3.

  • Ferritin. Screens for iron overload disorders

  • Homocysteine (High homocysteine levels may affect bone remodeling by increasing bone resorption (breakdown), decreasing bone formation, and reducing bone blood flow.) (Vacek, 2013)

  • Prolactin (screens for endocrine disorder)

  • Protein Electro.S (screens for multiple myeloma)

  • PTH Intact+Calcium, Ionized (screens for hyperparathyroidism)

  • Total Testosterone, Bioavailable Testosterone, Free testosterone especially in young men with osteoporosis.

Several of these tests like CBC, Blood chemistry, Vitamin D3, Thyroid function, and Homocysteine may be considered as ongoing osteoporosis prevention panel in people at higher risk or people who have developed pre-osteoporosis (osteopenia).

Putting it together

Bone remodeling is a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. Close cooperation between these two cell types along with the action of several molecules (ie. OPG, OPGL, RANKL, TGF-Beta, Vitamin D, Vitamin K2, magnesium, PTH, estrogens) are needed to achieve proper rates of growth and differentiation required for physiological processes.

Osteoclasts resorb and break down bone while osteoblasts build up bone mainly by releasing a hormone osteocalcin. Osteocalcin stimulates a hormone called calcitonin which thereby pushes hydroxyapatite into the bone. Calcitonin is secreted by the parafollicular cells of the thyroid gland in humans. It acts to reduce blood calcium, opposing the effects of parathyroid hormone.

And then there is the substance that helps build bone including calcium, hydroxyapatite, and type 1 collagen.

You can see now that addressing bone physiology involves reducing fall risk, reducing risk factors, nutrition and nutrient health, hormonal stability, and a whole lot of inflammation control.

If diagnosed with osteoporosis or bone density disorders (especially early in life) it is important to make sure secondary causes of osteoporosis are explored.

In part 2 we will go into treatment strategy.


Erlebacher A, Filvaroff EH, Ye JQ, Derynck R. Osteoblastic responses to TGF-beta during bone remodeling. Mol Biol Cell. 1998 Jul;9(7):1903-18. doi: 10.1091/mbc.9.7.1903. PMID: 9658179; PMCID: PMC25433.

Hall, J. E., & Guyton, A. C. (2011). Guyton and Hall textbook of medical physiology.

Ito, T., & Jensen, R. T. (2010). Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Current gastroenterology reports, 12(6), 448–457. https://doi.org/10.1007/s11894-010-0141-0

Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 22.3, Collagen: The Fibrous Proteins of the Matrix. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21582/

Pizzorno, L., & Wright, J. V. (2011). Your bones: how you can prevent osteoporosis & have strong bones for life-- naturally. Mount Jackson, VA: Praktikos Books

Schnell, S., Friedman, S. M., Mendelson, D. A., Bingham, K. W., & Kates, S. L. (2010). The 1-year mortality of patients treated in a hip fracture program for elders. Geriatric orthopaedic surgery & rehabilitation, 1(1), 6–14. https://doi.org/10.1177/2151458510378105

van Ballegooijen, A. J., Pilz, S., Tomaschitz, A., Grübler, M. R., & Verheyen, N. (2017). The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review. International journal of endocrinology, 2017, 7454376. https://doi.org/10.1155/2017/7454376

Vacek, T. P., Kalani, A., Voor, M. J., Tyagi, S. C., & Tyagi, N. (2013). The role of homocysteine in bone remodeling. Clinical chemistry and laboratory medicine, 51(3), 579–590. https://doi.org/10.1515/cclm-2012-0605

Vetter T, Lohse MJ. Magnesium and the parathyroid. Curr Opin Nephrol Hypertens. 2002 Jul;11(4):403-10. doi: 10.1097/00041552-200207000-00006. PMID: 12105390.

Wright, N. C., Looker, A. C., Saag, K. G., Curtis, J. R., Delzell, E. S., Randall, S., & Dawson-Hughes, B. (2014). The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 29(11), 2520–2526. https://doi.org/10.1002/jbmr.2269

Wu, D. J., & Adamopoulos, I. E. (2017). Autophagy and autoimmunity. Clinical immunology (Orlando, Fla.), 176, 55–62. https://doi.org/10.1016/j.clim.2017.01.007

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