This article and protocol are for informational purposes only, and not intended as medical advice. Please read the medical disclaimer below, and consult with your personal health care provider prior to taking supplements and acting upon the information provided in this article, protocol, or website. 

Discussion

Most people experience a bone fracture sometime in their lives. Bone fractures are very common, with approximately 8 million bone fractures occur in the United States each year. Most bone fractures can heal on their own if the broken ends are close to each other, and the bones immobilized with a cast, so that inherent bone mending can take place. Occasionally, surgery is needed to “pin” the bones in place, to allow for re-approximation of the fractured ends.

Depending upon proper re-approximation and immobilization of the fractured bone, It takes approximately 6 to 8 weeks for most fractures to heal. This does not mean the healed bone is back to its normal strength, as before the fracture, it simply means that one can usually use that bone for (arm, leg, etc.), for non-strenuous purposes. It will be several additional months for normal bone strength to return.

Three Main Stages of Bone Healing

Inflammatory Phase:  First 48 Hours.  At the time of the break, blood vessels in the bone are broken, causing bleeding which then forms a clot. The clot stops the bleeding, and via release of cytokines, the immune system’s white blood cells are triggered to infiltrate the area. White blood cells release peroxides and additional cytokines; all this being the inflammatory process.

Repair Phase:  Two Days – Three Weeks.  Chondrocyte cells form cartilage at the edge of the fractured bone tips, which is known as a callus. (Cartilage is made of collagen, elastin, and proteoglycans.) As the cartilage is being constructed on the edges, and extend out to the opposing fractured edge, mineralization with calcium, phosphorus, and magnesium, is occurring simultaneously. The soft bony calluses on each bone edge slowly grows to meet each other, creating a cartilage-soft bony bridge between the fractured edges. This soft bony callus bridge stabilizes the fracture, and creates the framework whereupon additional calcification can take place to heal and strengthen the bone. This process takes place due to the creation of new micro blood vessels (angiogenesis) that form around the cartilage, which supply oxygen and micronutrients. (There are no blood vessels within cartilage. Oxygen and micronutrients diffuse through cartilage to reach chondrocytes.)

Bone Remodeling Phase:  Three Weeks – 12 Weeks.  The soft bony callus of cartilage is replaced by solid bone, as mineralization with calcium, phosphorus, and magnesium continues to be incorporated into the callus. Vitamin K2 triggers osteoblasts (bone cells) to utilize calcium from the bloodstream and insert it into the bone matrix. A balance of both strength and flexibility is attained by a combination of minerals with collagen and elastin. The majority of the bone strength is restored after three to four months after the break, but it will take several additional months for the bone in the area of the fracture to be restored to its original strength.

Impaired Bone Healing

Five to ten percent of bone fractures fail to heal on their own. Most fail during the bone remodeling phase. There is a nonunion of the two ends of the bone fractures. This could be due to lack of bone re-approximation, where the two ends cannot physically reach each other. There could be a lack of adequate growth of soft callus (cartilage), to where a bridge is not created. Or, a lack of healing could be due to a lack of mineralization, or hardening of the soft callus.

A lack of cartilage growth or mineralization of the soft callus, could be due to a lack of angiogenesis. Without an adequate blood supply, micronutrients are not supplied for healing. Or, there could be adequate microvacularization, but a lack of calcium depositon/incorporation, or replacement of the soft callus by the osteoblasts.

Risk Factors for Bone Fractures Not Healing

1. Complex Fracture-  Bone fragments not re-approximated, not allowing bony calluses to join to form bridge.
2. Lack of Stabilization-  Bony callus re-approximation bridge continually disrupted due to lack of immobilization. For example, no cast, or walking on broken foot, and not allowing edges of bones to mend.
3. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)-  Long-term, high-dose use of some NSAIDs, inhibits bone healing up to 25%. Prostaglandins (PGE2), produced by the COX-2 enzyme, play an important role in bone remodeling. Certain NSAIDs, particularly COX-2 inhibitors, inhibit the endochondral ossification pathway, that is, the bone calcification that replaces cartilage of the soft callus. If NSAIDs are used only during the peri-operative period (before, and a few days after the fracture), there seems to be no significant slowing of bone healing. Ibuprofen has less of a deleterious effect than other NSAIDS, such as naproxen. There is debate regarding if, and by how much aspirin may delay bone healing. The studies are mixed. Examples of NSAIDs are:
   • Aspirin
   • Ibuprofen (Motrin, Advil)
   • Naproxen (Aleve, Anaprox, Naprelan, Naprosyn)
   • Celecoxib (Celebrex)
   • Diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)
   • Indomethacin (Indocin)
   • Oxaprozin (Daypro)
   • Piroxicam (Feldene)
4. Immuno-suppressants-  Immuno-suppressant medications (including corticosteroids) slow bone healing by inhibiting the production of prostaglandins, which are needed during the remodeling process of bone healing.
5. Anti-Coagulant Medications-  Warfarin, heparin, and aspirin impede bone metabolism and bone healing. (There is debate regarding if, and by how much aspirin may delay bone healing. The studies are mixed.)
6. Smoking-  Smoking not only delays bone healing, it also increases the risk of fractures in the first place. The negative effect of smoking on bones persists long after a smoker stops smoking, due to adverse effects on the bones. Nutritional supplements can help with the recovery from smoking’s negative effects.
7. Diabetes-  Due to damaged/scarred blood vessels from oxidative damage caused by high blood sugar levels. Therefore, a lack of oxygen and micronutrients are inhibited for the healing of the fractured bone. This is the same reason for diabetic neuropathy, kidney damage, macular degeneration, and many other diabetes complications.
8. Rheumatoid Arthritis- Aside from the immuno-suppressants/corticosteroids and NSAIDs used for managing rheumatoid arthritis (RA), RA itself delays the bone healing process due to excessive oxidative damage to the cartilage in the soft callus.

Since Many Antioxidants Also Reduce Inflammation, Won’t They Delay Bone Healing?

The short answer is, “no, antioxidants do not delay bone healing!”

Antioxidants neutralize free radicals, and therefore counter oxidative stress/damage. Oxidative stress/damage is not the same thing as inflammation, however, the two are connected. Oxidative stress/damage can cause inflammation, and inflammation increases free radical, oxidative stress.  Oxidation is caused by free radicals, and inflammation is a result of inflammatory biochemical processes from the immune system (cytokines, peroxides, etc. from white blood cells).  The point, antioxidants reduce oxidative stress, and therefore, indirectly reduce inflammation. Some antioxidants, such as grape seed extract and curcumin, reduce inflammation both directly and indirectly.

The question becomes, if inflammation is needed as part of the bone healing process (for the production of prostglandins for use during the endochondral ossification pathway), then won’t the use of antioxidants, particularly grape seed extract, curcumin, and others that have COX-2 anti-inflammatory effects, delay bone healing? The surprising answer is no!

If COX-2-inhibiting NSAIDs, like naproxen, slow bone healing, why wouldn’t grape seed extract, which also exhibits COX-2 inhibitory action also slow bone healing? The answer is, that antioxidants also have several other bio-chemical effects, other than anti-inflammatory effects. Bone healing following a fracture involves specific molecular signaling pathways, the expression of proteins, and the regulation of key cytokines. The medical studies are clear, various antioxidants have bone-healing properties by their positive effect on all these factors.

Antioxidants Support Bone Fracture Healing

Antioxidants either directly, or by counteracting the action of oxidative stress, contribute to activate the differentiation of osteoblasts (bone forming cells), mineralization process, and the reduction of osteoclast (bone resorption cells) activity. Not only has antioxidant supplementation not been shown to delay bone healing, various antioxidants have been shown to promote bone healing and bone strength.

In an animal study published in the Journal of Orthopaedic Surgery and Research in 2019, the effects of grape seed extract was studied for its effects on bone healing.(1) Grape seed extract was found to improve and accelerate bone healing, by improving bony callus formation, fracture union, and bone remodeling compared to the control group. Grape seed extract was also shown to enhance both bone healing and bone strength.

Grape seed extract suppresses excessive oxidative stress seen in rheumatoid arthritis, and inhibits bone destruction seen with this autoimmune disease.(2) Grape seed extracts ability to suppress excessive oxidative stress may be one of the mechanisms by which it creates an environment conducive to enhanced bone fracture healing. Grape seed extract protects against osteonecrosis (bone destruction) seen with corticosteroid use.(3)

Grape seed extract promotes bone strength, and inhibits bone resorption, by inhibiting effects of osteoclastic peroxide activity.(4, 5) In other words, it promotes bone strength in those with or without fractures. This is beneficial effect in protecting against osteoporosis, and it is beneficial effect for promoting bone healing following bone fracture.

Vitamin C promotes collagen formation. Collagen is a major component of cartilage, and the soft bony callus that is needed to form a union of the fracture ends (the bridge), is dependent upon the synthesis of collagen.

The beneficial effects of antioxidants on bone healing is not limited to grape seed extract. Vitamin E has been shown to enhance bone healing, as manifested by earlier bridging of the fracture line (union), more solid mineralization, and remodeling of bony callus.(6, 7)

Curcumin, the active component of turmeric, has a variety of pharmacological activities. Curcumin has been found to have a positive effect on bone healing, and specifically bone remodeling.(8 – 10) Excessive free radical oxidative stress found in those with type 2 diabetes can disrupt normal bone metabolism and greatly impair bone regeneration. Curcumin has beneficial effects on bone healing under diabetic conditions.(11)

In the bone, cartilage, and teeth, vitamin K2 binds with osteocalcin, causing osteoblasts (bone cells) to incorporate calcium into those tissues.(12) Vitamin K2 supplementation not only helps with growth, development, and maintenance of strong bones, it also helps prevent, and possibly help reverse osteoporosis.(13 – 15) For more on the benefits of vitamin K2, please refer to my article on my public website by clicking here.

Cells Create and Maintain Bone and Cellular Nutrition is Necessary for Bone Healing

Cells build and repair bone. Osteoblasts are the cells that lay down new bone, i.e., allow for mineralization of bone. Osteoclasts are cells that resorb bone, to free up minerals for use elsewhere in the body. In effect, the bones are a storage tissue of calicum, phosphorus, and magnesium. New bone matrix is continually being created by osteoblasts and resorb bone, and release minerals. A proper balance of osteoblast and osteoclast activity is needed to maintain strong, healthy bones. During remodeling of bone following bone fracture, osteoblast activity is increased and osteoclast activity is suppressed in the area of healing.

Cells require micronutrients to function. Osteoblasts are kicked into high gear during bone healing. Cellular structures are active, including enzymes, as these cells lay down calcium and magnesium to replace the cartilage callus. Proper cellular nutrition with diet and nutritional supplementation are needed to nourish, protect, and renew cells.

Mitocondria within osteoblasts create ATP for the increased energy needed during the repair process. Endogenous antioxidant enzymes are required to protect the cells from potential free radical damage due to increased metabolic processes. There is an increased need for micronutrients to meet the increased metabolic demand.

An abundance of micronutrients are needed to nourish the osteoblasts, protect the cells and cartilage, as well trigger renewal of mitochondria (mitophagy), and endogenous antioxidant enzymes. Supplemental co-enzyme Q10 and alpha lipoic acid are among the micronutrients that have been found to be beneficial in supporting osteoblastic activity, thereby supporting the acceleration of bone healing.(16)

In fact, the bone fragility seen with the use of bisphosphonate drugs in women with osteoporosis, is associated with compromised co-enzyme Q10 status.(17) This is an example of the importance of coQ10 for bone remodeling, bone strength and maintenance.

Equiscope® Electro-Therapy Accelerates Bone Healing

Electrical stimulation is a common adjunct used to promote bone healing following a bone fracture. However, not all electrical stimulation technology is the same. This is why there are mixed conclusions regarding the efficacy of electro-therapy. Some promoted electrical therapies are a complete sham, and are completely ineffective. Other electrical therapies provide minimal benefits in the acceleration of bone healing. However, one electrical therapy device of which I have personal knowledge and experience, is the Electro-Equiscope^{®, provided by the Thorp Institute (Encinitas, California).}

In fact, the bone-healing technology was so successful in shortening the healing time after my wife broke her back, she purchased the device and became an electro-therapist. She now treats various injuries and pain, supporting the healing process of others. If interested, please CLICK HERE to read my article about this advanced healing technology.

When electro-therapy is combined with quality nutritional supplements, the healing process is optimized, and pain is reduced.

Conclusion

Many micronutrients are beneficial in building and maintaining bone strength, including, but not limited to calcium, magnesium, vitamin D, vitamin K2, vitamin C, grape seed extract, curcumin, soy isoflavones, as well as many other polyphenols. It is clear that micronutrient supplementation supports bone healing, bone strength, and bone maintenance, and a quality nutritional supplement protocol should be considered for enhancing the healing of bone fractures.

Supplement Protocol To Support the Healing of Bone Fractures 

This article and protocol are for informational purposes only, and not intended as medical advice. Please read the medical disclaimer below, and consult with your personal health care provider prior to taking supplements and acting upon the information provided in this article, protocol, or website.

Minimal Protocol To Support Healing of Bone Fractures

Basic Protocol To Support Healing of Bone Fractures

Average Protocol To Support Healing of Bone Fractures

Advanced Protocol To Support Healing of Bone Fractures

• • AM: Morning with, or soon after breakfast; but not on empty stomach
  • Noon: At lunchtime with food, or shortly thereafter
  • PM: Late afternoon with food, or at, or after dinner
  • Please see my list of ingredients (below) that I like to see provided by a foundational vitamin and mineral supplement, as well as what is in the liver health supplement I use.
  • Magnesium, Calcium, and Vitamin D3 supplement. Since most people get a significant amount of calcium in their diet, but are very deficient in magnesium, a supplement that provides a 1:1 ratio of magnesium-to-calcium is in order. Four tablets per day (two in AM and two in PM), would provide at total of 500 mg of magnesium and 500 mg of calcium. One should consider boosting supplementing with an additional 500 – 750 mg of calcium per day beyond this for approximately four months after the fracture; for a daily total of 1000 – 1500 mg per day.  (Do not forget that there is a daily total of 250 mg of calcium provided in four tablets of the foundational mineral supplement.)
  • Vitamin K2 is usually found in a foundational multi-mineral supplement, and it is also provided as a stand-alone product, usually as 180 mcg tablet. Taking at least one per day is for preventative use; that is to prevent cardiovascular disease.
  • Joint Support Supplement that provides at least glucosamine and Meriva-brand curcumin. This supplement helps with cartilage synthesis, which is what the bony callus is made of.
  • Liver Support Supplement providing Milk Thistle Extract, N-Acetyl-L-Cysteine, Alpha-Lipoic Acid, Broccoli Extract, Turmeric Extract (Curcumin), Olive Extract, Green Tea Extract, Biotin, which not only protects and supports the functions of the liver, but also that of the brain, eyes, heart, lungs, kidneys, bladder, breasts, prostate, bowels, skin, immune system, and joints.
  • Probiotics providing at least take 12 billion colony-forming bacteria, providing Lactobacillus rhamnosus LGG® and Bifidobacterium BB12®, taken every-other-day or daily.  Probiotics help support absorption of micronutrients, including vitamin K2.
  • Melatonin is a sleep aid, in that it maintains circadian rhythms, by helping the brain to get into REM (dream state) sleep, for restoration of body and mind (as well as mood). However, melatonin is a powerful antioxidant, that works throughout the brain and body, including supporting bone strength and maintenance.
  • DHEA stimulates bone healing via supporting osteoblastic activity.  You can obtain DHEA from Douglas Labs by first creating a customer account by CLICKING HERE.  (If this link does not work for you, simply type “douglaslabs.com/patient-account” into a new browser tab.) Please use Referral Code 2074214. After you get your customer account, then search for DHEA on the website.

Ingredients that I like to see provided collectively by vitamin-antioxidant & chelated mineral tablets

Vitamin A, mostly as Beta Carotene
Vitamin C
Vitamin D3
Vitamin E
Vitamin K (K1 & K2)
B-Complex Vitamins
Curcumin (turmeric extract)
Quercetin
Green Tea Extract
Olive Extract
Rutin
Resveratrol
Choline
Lutein
Lycopene
N-Acetyl-L-Cysteine (NAC)
Calcium
Magnesium
Iodine (as potassium iodide)
Zinc
Selenium
Copper
Manganese
Chromium
Molybdenum
Including Ultra Trace Minerals

Medical Disclaimer:

Information on this website, written, spoken, or in any other communication by Dr. Ladd McNamara or any other information or reference is for informational purposes only. The information provided on this website is a result of years of practice, experience, and study by the author. This information is not intended as a substitute for the advice provided by someone’s personal licensed physician or other healthcare professional, or any information contained on or in any product label or packaging. Do not use the information on this website, or any other form of communication from Dr. Ladd McNamara or the Dr. Ladd VIP Program, for diagnosing or treatment of a health issue or disease, or for the prescribing of medication or the use of supplementation without a discussion with your licensed health professional first.  At best, the information provided on this website is only meant to supplement information provided by your own doctor or health professional, not to replace medical advice.  The information from this website is not meant to cover all possible uses, precautions, interactions or possible adverse effects of nutritional supplements with or without medications, or in conjunction with specific medical conditions.  The information from this website may not fit your specific health circumstances.  Never delay seeking medical care or disregard advice from your health care professional because of information you have received directly or indirectly from this website, from the Dr. Ladd VIP Program, or from Dr. Ladd McNamara himself.   Always speak with your physician or other healthcare professional before making any changes to your medication or embarking on a nutritional, herbal or homeopathic supplement program, or before using any treatment for a health concern. If you have, or suspect that you have, a medical problem, contact your health care provider promptly.  Do not disregard professional medical advice or delay in seeking professional advice because of something you have read or heard on this website, or due to any other information from Dr. Ladd McNamara or his representatives. Information provided on this website or the V.I.P. Program, and the use of any products or services mentioned on this website (or as a result of information provided this program, article, or website) by you DOES NOT create a doctor-patient relationship between you and Ladd McNamara, M.D.  Information and statements regarding dietary supplements have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease.

References

1. Gurger M, et al. Grape seed extract supplement increases bone callus formation and mechanical strength: an animal study. J Orthop Surg Res. 2019 Jul 5;14(1):206.
2. Park J-S, et al. Grape-seed proanthocyanidin extract as suppressors of bone destruction in inflammatory autoimmune arthritis. PLoS One. 2012;7(12):e51377.
3. Song Q, et al. Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis. J Orthop Sci. 2015;20(1):196–204.
4. Ishikawa M, et al. Grape seed proanthocyanidins extract promotes bone formation in rat’s mandibular condyle. Eur J Oral Sci. 2005;113(1):47–52.
5. Zhang Z, et al. Grape seed proanthocyanidins inhibit H2O2-induced osteoblastic MC3T3-E1 cell apoptosis via ameliorating H2O2-induced mitochondrial dysfunction. J Toxicol Sci. 2014;39(5):803–813.
6. Paskalev MD, et al. Antioxidant and bone healing effect of vitamin E in an experimental osteotomy model in dogs. Comp Clin Pathol. 2011;20(4):403–408.
7. Mohamad S, et al. The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model. Clinics (Sao Paulo) 2012 Sep; 67(9): 1077–1085.
8. Rohanizadeh R, et al. Therapeutic actions of curcumin in bone disorders. Bonekey Rep. 2016;5:793.
9. Li G, et al. Curcumin Promotes Femoral Fracture Healing in a Rat Model by Activation of Autophagy. Med Sci Monit. 2018; 24: 4064–4072.
10. Bose S, et al. Effects of PCL, PEG and PLGA polymers on curcumin release from calcium phosphate matrix for in vitro and in vivo bone regeneration. Mater Today Chem. 2018 Jun; 8: 110–120.
11. Li Y, et al. Sustained curcumin release from PLGA microspheres improves bone formation under diabetic conditions by inhibiting the reactive oxygen species production. Drug Des Devel Ther. 2018; 12: 1453–1466.
12. Myneni VD, Mezey E. Regulation of bone remodeling by vitamin K2. Oral Dis. 2017 Nov;23(8):1021-1028.
13. Rønn SH, et al. Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. Eur J Endocrinol. 2016 Dec;175(6):541-549.
14. Huang ZB, et al. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2015 Mar;26(3):1175-86.
15. Koitaya N, et al. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab. 2014 Mar;32(2):142-50.
16. Varela-López A, et al. Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition. Nutrients. 2017 Feb 22;9(2). pii: E176.
17. Kalyan S, et al. Nitrogen-bisphosphonate therapy is linked to compromised coenzyme Q10 and vitamin E status in postmenopausal women. J Clin Endocrinol Metab. 2014 Apr;99(4):1307-13.

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