Osteoporosis and Bone Health : Part 2

“To thrive in life, you need three bones. A wish bone, a back bone, and a funny bone”

-Reba McEntire


“Eat more calcium, take a calcium and vitamin D supplement, add some weight-bearing exercise, and if things don’t improve, we will consider a bisphosphonate.”



These recommendations are heard so often in doctors’ offices all over the world when discussing bone density issues that it is a surprise that I am even writing this article.


Yet, while these recommendations provide a scaffolding for a way to prevent worsening of bone density and perhaps even improve bone density, they lack a deep understanding of what the research tells us about the best ways to reverse bone density disorders.


After being given a diagnosis of osteopenia or worse, osteoporosis, we are often left wondering about the real impact of the diagnosis. We are also left wondering about which treatment recommendations are the most effective. After digging into the research, we find that many nutrients, hormones, diet, and lifestyle factors are involved with proper bone remodeling. It’s not a simple cookie-cutter answer. We also find that factors such as muscle mass and muscle quality (see Sarcopenia and Osteoporosis) are significant when preventing consequences of bone density disorders. And, we find that the conventional diagnosis and treatment of osteopenia and osteoporosis are fraught with controversies.


In part 1 of this series, we discuss background information of bone physiology and the underlying mechanisms involved with osteopenia and osteoporosis. In this series, we will look at actionable items to help prevent, slow, or possibly reverse bone density concerns and reduce fracture risk.


The understanding of treatment always begins with the pathophysiology and consequences of a disease. Knowing what happens (i.e., pathophysiology) will guide diagnosis and what is needed to reverse it.


Dexa Scans and T-scores


The diagnosis of bone density disorders has traditionally been done by Dual X-ray absorptiometry (DEXA), which measures the amount of bone mineral contained in a certain volume of bone by passing x-rays with two different energy levels through the bone (hence “dual”). Two scores – the T-score and Z-score – are given to help determine bone density. The T-score is a comparison of a person's bone density with that of a healthy 30-year-old of the same sex. The Z-score is a comparison of a person's bone density with that of an average person of the same age and sex. These scores are based on a standard deviation from the norm. If your T-score is -2.0, that means your bone mass is 20% less than average 30-year-old. The Z-score is typically used in diagnosing secondary osteoporosis and is always used for children, young adults, women who are pre-menopausal, and men under age 50. Since the focus of this article is geared toward primary osteoporosis, we will focus on T-score. Please note: there are other emerging diagnostic tools (i.e., QCT) that are not widely available to the general public at this point and are therefore not discussed in this article.


A normal T-score is anywhere from -0.9 to +4.0. Osteoporosis is diagnosed when a T-score is -2.5 or more. Osteopenia is diagnosed when a T-score is between -1.0 and -2.4. What makes this more complicated is that a person could have a completely normal bone density in their hips, femur, and forearm, yet their spine may be osteoporotic.


If bone density is low, it means that there is likely more osteoclastic (bone breakdown) activity then osteoblastic (bone building/preserving) activity. It likely means an adult has low efficiency of bone remodeling compared to bone breakdown (osteolysis).


Fracture Risk Algorithm


Enter the World Health Organization fracture-risk algorithm (FRAX). As we discussed in part 1, the bone density evaluation is only as important as the risk of fracture. The FRAX estimates the 10-year probability of a fracture and is used in combination with the DEXA to guide treatment recommendations.


The FRAX Calculation Tool uses factors such as age, sex, weight, height, previous fracture, parental history of fractured hip, smoking status, current or past history of long-term glucocorticoid use, rheumatoid arthritis diagnosis, alcohol use more than 3 units per day, secondary osteoporosis risk, and finally femoral neck bone mineral density. The FRAX is used in combination with the DEXA score to guide treatment and determine severity.



The U.S. guidelines for Bisphosphonate medications in postmenopausal women and men 50 years and older is based on the following criteria:

· A hip or vertebral (clinical or morphometric) fracture

· T-score ≤ -2.5 at the femoral neck or spine after appropriate evaluation to exclude secondary causes

· Low bone mass (T-score between -1.0 and -2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture ≥ 3% or a 10-year probability of a major osteoporosis-related fracture ≥ 20% based on the US-adapted FRAX

· Clinicians’ judgment and/or patient preferences may influence treatment for people with 10-year fracture probabilities above or below these levels


There are other tools that may be considered to guide treatment such as N-telopeptide testing (Ntx), which is a marker of active bone turnover.


It’s important to realize that no diagnostic tool in isolation is perfect. FRAX is used as an isolated marker and sole predictor is unreliable for the needs of osteoporosis therapy. If FRAX guidelines alone were used, at least 72% of white women older than 65 years of age and 93% of women older than 75 would be recommended therapy. In comparison, with a DEXA scan alone, 35% and 43% of the same cohorts, respectively, would be recommended therapy (Hackenthal, The Osteoporois Controversy: Part II: Are we overtreating?, 2018).


Ideally decisions would be made based on DEXA, FRAX, and Ntx. The latter test, Ntx, can show how aggressive the bone turnover is at any given moment of time.


It is important to know that some people are being diagnosed in outpatient settings using less sophisticated means. Merck (the same company that markets bisphosphonates) introduced the use of peripheral bone density scanners into outpatient clinics. These scanners base an osteoporosis diagnosis on the bone density of hands and wrists rather than based on including joints that have the greatest consequence (hip and femur fracture). Subsequently, with the rates of Fosamax, use increased (Hackenthal, The Osteoporois Controversy: Part II: Are we overtreating?, 2018)


Bisphosphates and Related Controversies


If they meet the guidelines for therapy, patients are often given the option of starting Bisphosphonates. Although bisphosphonates may improve or slow a declining DEXA score, there are questions about the quality of bone that is being developed by bisphosphonates. The drug works by decreasing osteoclastic activity. While slowing osteoclasts may be a strategy for slowing bone breakdown, it is important to know that osteoclastic activity is needed for bone remodeling. Yet, by preventing osteoclastic activity, there are questions about whether or not this leads to healthy bone remodeling (Pizzorno, 2011).


Some evidence shows bisphosphonates are actually producing brittle bones. A landmark 2010 study stated that 1% of bisphosphonate users will experience a non-traumatic brittle bone fracture in the wrist or jaw osteonecrosis (Hackenthal, The Osteoporois Controversy: Part II: Are we overtreating?, 2018). Longer-term use of bisphosphonates has been associated with an atypical femur fracture as well. The risk of atypical fracture and osteonecrosis is 1 for every 100 fractures prevented for up to 5 years on bisphosphonates (Hackenthal,2018, part 2).


Reported side effects associated with bisphosphonates include bone pain and atrial fibrillation (Pizzorno & Wright, 2011).

It is believed that bisphosphates certainly have a greater role in patients that have already had a osteoporotic fracture. But what about people who have an early diagnosis of osteoporosis with no existing fracture and/or have been told they have osteopenia?


When given an osteoporosis diagnosis, most people are left with the sublime feeling of taking a pill that might not even help with a slight risk of it leading to side effects. Not the best option for most.


Here is where diet, lifestyle, nutrient, phytonutrient, and functional food recommendations can really impact outcomes and need to be implemented.


Now back to the pathophysiology and consequences of osteoporosis. We must find therapies that hopefully prevent falls, improve bone quality, and slow or stop bone loss.


Other Categories of Treatments

Denosumab (monoclonal antibodies against RANKL). This is the brand name Prolia. It was FDA approved in 2010. It works by inhibiting RANKL, thus slowing osteoclastic activity. It is used for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture or multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. It should be noted that osteonecrosis of the jaw and atypical femur fracture have been reported with the use of Prolia. In addition, there have been reports of multiple vertebral fractures upon the discontinuation of Prolia (Amgen, 2019).


Parathyroid Hormone Peptides (Teriparatide). The brand name is Forteo. It was FDA approved in 1987. It is used for treatment of postmenopausal women with osteoporosis at high risk for fracture. It is also used for men with primary or hypogonadal osteoporosis at high risk for fracture, and in treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture. It is noted that in rats, teriparatide caused an increase in the incidence of osteosarcoma, a malignant bone tumor (Liily, 2020).


Vitamin D Analogs (Alfacalcidol, calcitriol, eldecalcitol) have been approved for osteoporosis, and are likely most appropriate in populations who cannot normalize Vitamin D (25-0H, D3) levels through standard approaches. However, the use of calcitriol and Alfacalcidol is limited by their major side effect, hypercalcemia, which is mediated mainly by VDR activity in the small intestine.


While there are certain scenarios such as previous fracture and high FRAX score that make pharmaceutical interventions highly indicated, most people with an osteopenia and osteoporosis diagnosis can approach the disorder successfully with diet, lifestyle, and nutrient interventions. Next we will dive into these categories.


Exercise


I know you have heard it time and time again. Exercise, Exercise, and Exercise. If you are getting older, the problem is that if you are inactive and being told to exercise, it can be quite painful to start. Pounding on the pavement might not feel great on your feet, knees, and legs. Yet for exercise to have an impact, it needs to be weight bearing. Traditional light load exercises like biking and swimming may be good for muscle mass (important), but might not entirely impact bones in the same way that weight-bearing exercise does.


This does not mean you need to go from inactive to being a marathoner. Quite the opposite. What it means is that you can progressively challenge your body.


The importance of exercise goes beyond the need for stimulating bone. Exercise also prevents sarcopenia, which is the loss of quality and quantity of muscle. When thinking about fracture risk, having good muscle volume and muscle quality will certainly prevent falls. Imagine having to maintain your balance to protect yourself from a fall. This requires a bit of agility, a bit of strength, a bit of balance, and some minor athleticism. If dealing with osteopenia or osteoporosis, your exercise training should be geared toward muscle preservation, bone stimulation, balance, agility, and joint and muscle strength.


Another perfect exercise for the person with bone density concerns, especially osteoporosis, would be a movement-based exercise that is weight-bearing, preserves muscle, improves balance, and is fairly easy to perform. Hence, this is where Thai Chi really shines. Thai Chi has been researched in studies for osteoporosis and it fares well. Home video and streamed classes exist, as well as in-person sessions at local community centers and parks.


In addition, light-load power training using a Weight Vest is a great option for training. In studies, subjects were involved in a protocol that started with body weight deep squats, front lunges, side lunges, calf raises, and toe raises in 2 sessions per week. They progressed by using a weighted vest equal to about 10% of their current body weight (see Hypervest). This protocol is an excellent and safe way to incorporate weight-bearing exercise to improve bone mass density.


Jump roping appears to be an ideal exercise for osteoporosis prevention and treatment in more conditioned older adults who are able to tolerate its impact. Jump roping involves agility and footwork that is helpful in improving balance while also adding compressive forces (jumping) that may stimulate bone growth and repair.


The very least and probably most practical is resistance training, which ultimately trains the body for more joint strength. This can lead to improved muscle mass and fall prevention. More formal weight programs like Osteostrong have recently been introduced and provide a structured weight training regimen geared to improve bone density.


It cannot be overlooked that fall prevention is essential in anyone who has osteoporosis. Fall prevention strategies in the home, while exercising, while getting out of the car, and while using stairs should be employed.




While exercises are a foundation for good bone health and fall prevention, many nutrient interventions can also impact bone health.


Dietary Components for Bone health


Bone Health Micronutrients


Calcium and Vitamin D3



Calcium and Vitamin D3 are the mainstay nutrients most people consider when thinking about ways to improve bone health.


Calcium is an important part of an orchestra of nutrient factors that make up good bone health. And as you’ll read below, Vitamin D pairs with calcium because of its impact on calcium absorption. Even further in the article you will learn that Vitamin D pairs with Vitamin K2 to regulate Vitamin K’s activity in bone, arteries, and elsewhere. So the synergy of Calcium, Vitamin D, and Vitamin K2 are a definitive foundation of bone preservation and osteoporosis approaches.


The specific form of calcium supplementation seems to matter. Many older adults suffer from hypochlorhydria (low stomach acid aka hydrochloric acid) due the aging of the stomach mucosal layer and also sometimes due to use of chronic proton pump inhibitors. To absorb calcium, hydrochloric acid (hcl) must be available in adequate amounts in the digestive tract. Because of this, a citrate form of calcium will be better absorbed. In fact, Calcium citrate will generally be absorbed 45% more compared to other forms of calcium (Pizzorno & Wright, 2011).


Important sources of calcium in the diet are dairy products, fish (especially sardines with bones), pulses, nuts and seeds, and some fruits and vegetables. It is important to note that milk products are also a source of protein, calcium, vitamin D, zinc, phosphorus potassium, riboflavin, and B12 (all bone supportive nutrients). Fermented dairy products such as soft cheeses, yogurt, and kefir can add pre and probiotics which improve metabolism of calcium (Munoz-Garach & et.al, 2020). Milk consumption in observational studies of Caucasian and Asian populations has been linked to significant increase in bone density and reduced fracture risk (Munoz-Garach & et.al, 2020).


99% of the body's calcium is stored in the bones as hydroxyapatite. The rest of the calcium is bound in the blood or in free form (ionized) and is circulating in the body. If the blood levels are lower than what is needed for physiologic processes, then bone calcium is mobilized from bone (Valdurthy & et.al, 2016).



As mentioned, calcium regulation in the blood is largely controlled by Vitamin D and its interrelation with parathyroid hormone (PTH). Through a series of steps involving the liver and kidney, Vitamin D eventually becomes 1,25(OH)2D3 which interacts with the intestine to promote calcium absorption from our diet. The principal function of 1,25(OH)2D3 is the maintenance of calcium homeostasis and to increase calcium absorption for the intestine (Valdurthy & et.al, 2016).

Regarding age-related decline in the formation and function of 1,25(OH)2D3, Vitamin D3 often results in a secondary hyperparathyroidism of aging. Calcium absorption goes down in the gut and the bone calcium gets used more rapidly for body physiologic processes. In bone, both parathyroid hormone and 1,25(OH)D3 stimulate osteoclastogenesis, promoting osteoclastic bone resorption and decrease in bone calcium. Age-related decline in Calcium Absorption is related to age-related changes in certain intestinal calcium absorption pathways (TRPV6, Calbindin), changes in enzyme function (CYPR1, CYP24A1, CYP27B1), and changes in kidney function (Valdurthy & et.al, 2016).


There are also genetic variants in enzymes (CYPR1, CYP24A1, CYP27B1) that may influence calcium homeostasis. Moreover, variants that affect Vitamin D function include Vitamin D Receptor (VDR) Single Nucleotide Polymorphisms (SNPS) that may affect Vitamin D absorption.


Studies have shown that 800 IUs of Vitamin D3 combined with 1200-1400 mg of Calcium daily will increase 25(0H) Vitamin D levels greater than 20mg/ml levels in 97.5% of women (Valdurthy & et.al, 2016).


Vitamin K


Vitamin K2 is one of the more intriguing nutrients for bone health. There are three forms of Vitamin K (vitamin K1, vitamin K2, and vitamin K3). The K2 form is the primary form studied when it comes to bone health. Vitamin K2 is called Menaquinone and there are two subtypes: MK-4 and MK-7. The normal sources in the diet of MK-4 are poultry products, grass-fed butter, liver, and eggs. MK-7 is found in fermented products like Natto. It is also found in cheese from Greece (feta), Italy (gorgonzola), France (münster), and England (cheddar) due to the bacteria used. Vitamin K1 (phylloquinone) is rich in many green leafy vegetables. Vitamin K3 (menadione) is a synthetic provitamin that converts to MK-4.

The mechanism of Vitamin K2 is best understood by its ability to interface with many enzymes and proteins that involve bone formation, including Osteocalcin, Protein S, and Matrix GLA Protein (MGP).




Vitamin K2 helps with bone matrix formation during bone mineralization. It does this by acting as a cofactor for microsomal-gamma carboxylase. To understand this, we must first explain that carboxylated osteocalcin (as compared to de-carboxylated osteocalcin) is the needed state for bone mineralization. Osteocalcin is a hormone released by osteoblasts that is a signal of the bone remodeling process. When osteocalcin is carboxylated, calcium can move into the bone and help with remodeling. So, Vitamin K is a cofactor for microsomal gamma carboxylase that helps facilitate the conversion of glutamyl to gamma carboxyglutamyl residues in osteocalcin. In the gamma-carboxyglutamic state, osteocalcin binds calcium leading to bone mineralization (Munoz-Garach & et.al, 2020).

  • In addition, bone proteins interact with Vitamin K2 such as:

  • Protein S. Interfaces with Vitamin K2 to regulate osteoclasts activity.

  • Matrix GLA protein (MGP). This Vitamin K2-linked protein is involved with binding of hydroxyapatite crystals and organic crystals in bone.

  • Vitamin K2 decreases Receptor Activator of Nuclear Factor Kappa-beta Ligand (RANKL). This decreases osteoclast activity and promotes bone formation.

  • Vitamin K2 also protects against apoptosis of osteoblasts and thereby increases volume of osteoblasts.

MK-4 vs MK-7


While most bone-health directed Vitamin K2 supplements contain the MK-7 form, it’s important to note the difference. Studies in osteoporosis subjects involving Vitamin K2 have shown indeterminate but mostly positive benefits. It appears Vitamin K2-MK4 is possibly the better form for bone density improvement at about 45 mg daily, yet the positive studies were primarily studies that combined MK-4 with Vitamin D. (We will talk more about the interplay of Vitamin D and Vitamin K later). The MK-4 form of Vitamin K2 at 45 mg per day (taken with Vitamin D3) has shown to lower fracture risk and decrease bone loss in both non-osteoporotic post-menopausal women and osteoporotic post-menopausal women. The MK-7 form has also been studied mainly in Danish subjects and is thought to be of interest due to its longer half-life and better absorption compared to MK-4. In MK-7, the dosage showing the most effectiveness in increasing bone density after 3 years of supplementation is 180 mcg.


MK-7 has been considered the main form when looking at therapeutic reduction of arterial calcification.

The best choice is perhaps to choose a supplement that contains Calcium Citrate, Vitamin D3, MK-4, and MK-7.


Vitamin K2 and Vitamin D3 Synergy


Most studies (if not all) of Vitamin K2 show it works only when given with Vitamin D3. Vitamin D promotes the production of Vitamin K-dependent proteins as shown in rodent studies back in 1985. Also, in Vitro studies show that Vitamin D enhances Vitamin K-dependent bone protein concentrations and induces bone formation buy stimulating osteoblastic-specific genes. In ovariectomized rats (lacking estrogen), only Vitamin K in combination with Vitamin D prevented bone loss but not vitamin D alone. One other interesting and concerning aspect is that some research shows that Vitamin D and Calcium supplementation without Vitamin K may lead to a relative Vitamin K deficiency and a relative Hypercalcemia. An imbalance between Vitamin D and Vitamin C may promote calcification of the arteries (arterial hypercalcemia). This is when calcium goes into arterial vascular tissue instead of bone leading to atherosclerosis and osteoporosis (Van Ballegooigen & et.al, 2017).


Magnesium


Approximately 50-60% of the body’s total magnesium is found in bones. Magnesium plays an important role in bone formation as magnesium ions bind at the surface of hydroxyapatite crystals, improve the solubility of phosphorus and calcium hydroxyapatite, and induce osteoblasts.


Magnesium is needed for the activation of Vitamin D. Magnesium deficiency impairs parathyroid hormone secretion which is needed for activation of Vitamin D3. Low parathyroid hormone would ultimately decrease calcium absorption (Tabataba & Sellmeyer, 2021).


Chlorophyll (from green leafy vegetables), nuts and seeds, and water are the major sources of magnesium ( (Jahnen-Dechent, 2014). It's important to note that magnesium is notoriously hard to absorb. Magnesium Aspartate, Magnesium Gluconate, and Magnesium Glycinate are considered the forms with the best absorption.


Supplementation of Magnesium Citrate 1800 mg for 60 days in 20 postmenopausal women significantly increased osteocalcin, a marker of bone formation (Tabataba & Sellmeyer, 2021). Note: this is in excess of amount of magnesium that would typically be used and may lead to diarrhea.


Potassium

Dietary potassium may reduce acid load and therefore reduce calcium depletion from bones. Lambert et. al showed that potassium alkaline salt supplementation reduced renal excretion and acid excretion and also lowered N-telopeptide (Ntx) values (Munoz-Garach & et.al, 2020).


Strontium Citrate

Strontium is a mineral found in seawater and soil. The level of Strontium in food generally depends on the region where the produce is grown. Strontium is found in seafood, whole milk, wheat bran, meat, poultry, root vegetables, spinach, lettuce, carrots, peas, and beans. It came onto the scene in bone health most recently due to the use of a strontium analog called Strontium Ranelate that has been used in trials in Europe for osteoporosis. While showing some efficacy in improving bone density, Strontium Ranelate is fraught with concerning potential side effects including venous thrombosis, abnormal cognition, and seizures (Nieves, 2021). We know that Strontium is absorbed into hydroxyapatite, possibly making it improve bone density. However, it is unclear, at least at this time, if the deposit of strontium into bone actually improves bone quality. Many supplement companies market the use of Strontium citrate as adjunct to foundational osteoporosis supplement protocols. Proponents of Strontium Citrate state that strontium actually helps with calcium absorption and may have many mechanisms related to slowing osteoclast activity and that it’s not simply replacing calcium in the bone (Pizzorno, Osteoporosis, 2020). Most Strontium citrate regimens involve 680mg/day daily dose for osteopenia or osteoporotic populations.


Boron

Boron is present in several foods, fruits, legumes, nuts, eggs, and legumes. It has been shown in N=80 studies using 10 mg per day to increase free testosterone, lower hsCRP , and lower TNF-alpha. Again, this has an anabolic and anti-inflammatory effect on the body, which may affect bones (Naghi & et.al, 2011). Also, 3 mg of boron daily may theoretically decrease urinary calcium loss and activate 1,25 (OH)2D3 production and bone mineralization (Nieves, 2021). This overall effect increases calcium absorption. It is fairly easy to get 3 mg of Boron in the diet each day without supplementing

.

See this list:

  • Raisins, 4.51 mg of Boron/ 100 g. Almonds, 2.82 mg of Boron/ 100 g. Dried Apricots, 2.11 mg of Boron/ 100 g. Peanut Butter, 1.92 mg of Boron/ 100 g. Brazil Nuts, 1.72 mg of Boron


Other key Minerals and Nutrients :

While difficult to cover all the key nutrients that are involved with bone metabolism, it is important to point out other nutrients that are involved with bone signaling, inflammation control, and management of bone homeostasis. They include: Zinc, Manganese, Copper, Selenium, Silicon, Iodine, Vitamin C, Vitamin A, Vitamin E, Omega-3’s, B6, B12, Folate, Riboflavin, and Niacin. Most of the nutrients can be found in a good quality multivitamin which I believe is fair to say that most of us should be taking for preventative health reasons.


Macronutrients


Protein

Protein intake and its relationships to broader health have been discussed at length. Many diets have claimed that high amounts of animal protein in the diet compared to plant protein may make the pH of the body acidic, leading to bone leaching. The thinking was that high protein intake (especially more sulfur amino-acid containing animal protein) might lead to bone loss due to acid load. This was called the "Nutritional Acid Load Hypothesis.” However, the concept of protein in the diet is becoming slightly more sophisticated. It appears that protein in the presence of adequate calcium intake is beneficial for bone health (Munoz-Garach,2020). Protein and calcium appear to be synergistic in their impact on bone. Protein intake signals IGF-1 which is a pro-hormone for bone formation. IGF-1 improves calcium and phosphorus absorption in the digestive tract, helps with synthesis of calcitriol (vitamin D), and increases the rate of phosphate reabsorption from the kidney (Munoz-Garach & et.al, 2020). It’s now reasonable to suspect that inadequate protein intake would contribute to bone loss. Reasonable protein intake depends on level of activity, but most estimates say that an adult should be consuming 0.8 grams of body weight per day. Yet, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommends dietary protein intake of 1.0-1.2 kg/body weight/day with at least 20-25 grams of high-quality protein at each main meal.


Food groups like dairy (if tolerated) seem to be an ideal food for bone health as they are rich in calcium and protein. Also, it’s no surprise that tempeh and tofu and other soy products are also rich in protein and calcium and these foods are consumed frequently in populations with low rate of bone density concerns. It is important to note that soy also contains phytonutrients (isoflavones/phytoestrogens) that may be having a positive effect on bone health and bone fracture prevention.


It also important to note that protein can also enhance strength training, hypertrophy, and lean mass acquisition. These factors may ultimately prevent falls if they result in strength preservation.


Dried Fruits (Higgs & et.al, 2017)



Prunus domestica and Prunus salicina, which are the Latin names for prunes, would be considered a functional food item that is geared toward improving bone health. Prunes contain Vitamin K, boron, copper, potassium, quinic acid, and chlorogenic acid, all which may benefit bone health. In 2014, Hooshmal et. al showed that in postmenopausal women, 100 grams of prunes per day significantly improved Bone Mass Density of the ulnar bone and spine compared to those consuming dried apples. This was again shown by Hashmone et. al in 2016 in post-menopausal women ages 65-79 where consuming either 50 grams of prunes or 100 grams of prunes per day resulted in total bone mass density loss being significantly prevented compared to control. Trap-5B, which is a marker of bone reabsorption, was reduced by 3 months of this trial and sustained at 6 months. It is thought that prunes may suppress bone turnover by increasing growth hormone (Igf-1) and increasing receptor activity of NF-Kappa Beta Ligand (RANKL) while increasing osteoprotegerin (OPG) and inhibiting sclerostin. All of these pathways point to slowing or stopping bone breakdown or bone reabsorption. Receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of the nuclear factor-kappa B (RANK)/osteoprotegerin (OPG) system is the final common pathway for bone resorption. Osteoblasts and activated T cells in the bone marrow produce the RANKL cytokine. RANKL binds to RANK expressed by osteoclasts and osteoclast precursors to promote osteoclast differentiation. OPG is a soluble decoy receptor that inhibits RANK-RANKL by binding and sequestering RANKL.


Other Nutrients


DHEA


Dehydroepiandrosterone (DHEA) is a weak adrenal androgen. It is considered a precursor for estrogen (estradiol and estrone) and testosterone (at least in women). DHEA increases Transforming Growth Factor B (TGF-B2) in human osteoblasts which is evidence of stimulation of their activity. DHEA-sulfate (DHEA-S) has been shown in many studies as an independent marker for osteoporosis and osteopenia. There is a particular application for DHEA in post-menopausal women who have been exposed to long-term steroid use which predisposes this population to significant risk of osteopenia and osteoporosis. An elegant long-term study by (Papiereska, 2016) used DHEA supplementation as an add-on to an osteoporosis regimen for 19 women, 50-78 years of age who were each 2-years post-menopausal and had been on long-term steroids (at least 7.5 mg-15 mg daily of prednisone for at least three years prior to enrollment). Their baseline measurements included DEXA scans, IGF-1 (growth hormone), DHEA-S, and Calcitonin (a marker of osteoblast activity). For 1 year they were put on 1500mg of daily elemental calcium (from diet and supplements), Alfacalcidol .5 mcg daily, and 12.5-25mg of hydrochlorothiazide if they developed hypercalciuria. After year-1 the regimen added DHEA supplementation 25mg twice per day, and this was taken for a year. (Note: the baseline DHEA-S was low in all subjects). The outcomes were compared to baseline, year 1, and year 3. DHEA-S was measured at different intervals (6 weeks, 6 months) and doses were reduced by half if subjects exceeded 4000 ng/ml of DHEA-S levels.


The outcomes were as follows.

  • IGF- (growth hormone) increased from baseline of 102 +/- 26.9 mg/l after year 1 to 175+/- 66.3 mg/l after 6 weeks of DHEA to 213+/- 60 mg/l after 6 months. (p <.0001)

  • Osteocalcin increased from 11.3 +/- 6.0 mg/ml at baseline to 17.4 +/- 4.8 ng/ml at 6 weeks to 20.2 +/-7.1 ng/ml at 6 months (p<.001)

  • Bone Mass Density:

  • At 6 months lumbar spine BMD increased by 0.91 +/- 1.85% (P

  • At 6 months femoral neck BMD increased by 1.07 +/- 1.85% (P,.001) compared to year 1 protocol

  • At 12 months lumbar spine BMD increased 4.39 +/- 3.05% (p

  • At 12 months femoral neck BMD increased 2.55% +/- 3.05% (P,.001) compared to year 1

  • 17 of the 19 subjects had improved bone density

If one is to use DHEA as a supplement, it is important to periodically measure levels of DHEA-sulfate as levels can significantly increase and lead to acne and alopecia.


Probiotics


In observational studies it has been shown that probiotics alter Vitamin D3 levels and calcium absorption and slightly decrease bone loss in a similar capacity to Vitamin D supplements with or without calcium. The strain is unknown (Munoz-Garach & et.al, 2020). There is some evidence that specific strains fractures can help with healing certain fractures. In patients receiving probiotics exhibited a significantly faster pace of improvement than those on placebo. In elderly patients receiving Lactobacillus casei Shirota (YAKULT) at month showed faster fracture healing rates of a distal radius fracture compared to placebo. The probiotic group showed healing at month. 4 comparable levels with those of patients receiving placebo at month 6. (Lei M, 2016)

Melatonin

An emerging therapy that has been used in clinical trials for post-menopausal women is melatonin. It has been shown that postmenopausal women with osteoporosis generally have low melatonin levels. In addition, bone turnover in premenopausal women has been associated with low melatonin levels. Cell, animal, and human trials have elucidated a few mechanisms that show how melatonin might be working to slow bone loss and build bone. First it is considered a RANKL inhibitor, thus slowing osteoclastic activity. Second, it quenches the free radical Hydrogen Peroxide as an antioxidant so it may preserve bone density. It also has been shown to reduce inflammatory cytokines TNF-alpha, IL-6, and Interleukin 1-Beta. Finally, it has been shown in tissue studies to increased bone building properties like osteoprotegerin. One study used 1 mg at bedtime over the course of a year in postmenopausal women with osteopenia. Subjects saw a significant increase in BMD of the femoral neck. With 3 mg dosing over a year, the same population saw increase in BMD of the spine. If you have never taken melatonin it’s important to work up slowly. You can have vivid dreams when you start taking it and sometimes can wake feeling groggy (Li, 2019 ).

Sulforaphane

Sulforaphane-buffered bone issues were secondary to steroids in one trial. This is a really remarkable finding as many people with Autoimmune conditions are on chronic steroid use. Sulforaphane is an isothiocyanate occurring in stored form as glucoraphanin in cruciferous vegetables such as cabbage, cauliflower, and kale, and at high levels in broccoli, especially in broccoli sprouts. Glucoraphanin requires the plant enzyme Myrosinase to convert it into sulforaphane. It has a wide range of properties, including its role in preserving and increasing glutathione (antioxidant) status. Home sprouting is easy to do and Sulforaphane supplements are also available. This is one to consider for people who are focused on preventing bone loss secondary to steroid use (Hao, 2014).


Others:


Isoflavones/Phytoestrogens have been used in many trials. Due to the dramatically conflicting data, they are being left out of this discussion until further clarity is found about their effectiveness.


Combination Studies


Several trials have combined micronutrients and compared how they stack up against conventional treatment. Combination of Micronutrients for Bone (COMB) Study in 2011 showed a specific micronutrient protocol to be at least as effective for osteoporosis treatment as bisphosphonates and Strontium Ranelate. This protocol included daily vitamin D (2000 IU's), Docosahexaenoic Acid (DHA) 250mg, Vitamin K2 (MK-7) 100mcg, Strontium Citrate 680 mg, and 25 mg of elemental magnesium daily. In addition, the protocol encouraged adequate sources of dietary calcium and daily exercise.

The MOTS study for postmenopausal osteopenic women included daily melatonin 5mg, vitamin D 2000 IU's, Vitamin K2 60 mcg (MK-7), and Strontium Citrate 450 mg or placebo in a 1-year study of 22 patients. Average BMD in the MSDK group increased by 2.2% compared to -3.6% in placebo group. The FRAX risk of major vertebral osteoporotic fracture reduced by 6.48% compared to a 10.82% increase in risk in the placebo group. The left hip showed particular improvement. The study compared markers of osteoclastic activity/bone reabsorption such Collagen Type 1 Cross-linked telopeptide (Ctx) against markers of bone formation such as Procollagen type 1 amino terminal propeptide (P1NP) and Osteocalcin (OP). In the first 6 months, the study group showed an increase in P1NP yet not Osteocalcin. The effect on Ctx was not significant. (Maria & et.al, 2017)


Whenever learning about an isolated condition like osteoporosis, it’s important to contextualize the information. If in full blown osteoporosis, the information discussed here should be a top priority for consideration, combined with data and treatment approaches for any other conditions you are dealing with. This is especially true if you are in a higher risk group for a fall. For someone reading this that is more concerned about preventative aspects, the information in this article need not compete with other dietary or lifestyle strategies but rather complement or supplement what you are doing.

I think about a life well lived into old age and the values and lifestyle that would be most enjoyable at that stage of life. Bone health can certainly be the difference maker at that stage of life as it relates to quality and quantity of life.


With the emergence of understanding about other key nutrients like Vitamin K2, Vitamin D, melatonin, and muscle mass preservation, it will be exciting to see if the numbers of osteoporotic-related fractures start to decline and that fractures decrease in our older populations overall.


If you would like to see my bone health protocol click here and look in protocol section.


Works Cited


Amgen. (2019). Prolia Highlights and Prescribing Inofmration. Retrieved from https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/prolia/prolia_pi.pdf


Hackenthal, V. (2018, April 2). Osteoporosis Controversy: Part 1: Are we over-screening? Retrieved from Rheumatology Network: https://www.rheumatologynetwork.com/view/osteoporosis-controversy-part-i-are-we-over-screening


Hackenthal, V. (2018, April 4). The Osteoporois Controversy: Part II: Are we overtreating? Retrieved from Rheumatology Network: https://www.rheumatologynetwork.com/view/osteoporosis-controversy-part-ii-are-we-over-treating


Hao, L. .. (2014). Sulforophane Reverses Glucocorticoid induced apoptosis in osteopblastic cells through regulation of NRF2 pathway. Drug. Des. Dev. Ther, 8: 973-982.


Higgs, J., & et.al. (2017). Nutrition and Osteoporosis Prevention For the Orthopedic Surgeon: A wholefoods approach. Efort Open Reviews, Vol 2. No. 6. P. 300-308.


Jahnen-Dechent, W. &. (2014). Magnesium basics. Clinical kidney journal, 5(Suppl 1), i3–i14. https://doi.org/10.1093/ndtplus/sfr163.


Lei M, H. L. (2016). he effect of probiotic treatment on elderly patients with distal radius fracture: a prospective double-blind, placebo-controlled randomised clinical trial. Benef Microbes., Nov 30;7(5):631-637. doi: 10.3920/BM2016.0067. Epub 2016 Sep 16. PMID: 27633174.


Li, T. E. (2019 ). Melatonin: Another avenue for treating Osteoporosis. J. Pineal Resr., 66:e12548.


Liily, E. (2020). Forteo Highlightes and Prescribing Information. Retrieved from https://pi.lilly.com/us/forteo-pi.pdf


Maria, S., & et.al. (2017). Melatonin-micronutrents osteopenia treatment studdy (MOTS): A translational study assessing Melatonin , Strontium citrate, Vitamin D3, and Vitamin K2 (MK7) on bone density, bone maker turnover, and health quality of life in postmenopausal osteoenic women. Aging, Jan 26:9(1) 256-283.


Munoz-Garach, A., & et.al. (2020). Nutrient and Dietary Patters related to Osteoporosis. Nutrients, 12(7):1986.

Mynenin, V., & Mezey, E. (2017). Regulation of Bone Remodeling by Vitamin K2. Oral Diseases, 23, 102-108.


Naghi, M., & et.al. (2011). Comparitive effects of daily and weekly Boron supplemenation of daily and weekly Boron supplemenaton on plasma steroids and proinflammatory cytokines. JNL of trae elements in medicin and bilogy . Ogranzation of the sciety for minerals and trace elements, Jan;25(1):54-8.


Nieves, J. (2021). Marcus and Feldemens Osteoporosis , 5th edition. London: Elsevier/Academic Press.

Papiereska, L. e. (2016). Effects of DHEA supplementation on IgF-1, osteocalcin, and bone mineral deinsity : post menopausal , glucocorriticoid women. Advances in Medical Sciences , 57(1):51-7.


Pizzorno, L. (2020). Osteoporosis. In J. Pizzorno, & M. Murray, The Textbook Of Natural Medicine 5th edition (pp. 1642-1645). Elsevier.


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


Tabataba, L., & Sellmeyer, D. (2021). Nutritional Supplements in Skelatal Health. Curretn Osteoporosis Research, 19(1) 23-32.

Valdurthy, V., & et.al. (2016). Vitamin D Calcium Homeostasis And Aging. Bone Research, 4,16041.


Van Ballegooigen, A., & et.al. (2017). The Synergistic Interplay between Vitamin D and K for Bone and Cardiovascular Health. A Narrative Review. International Journal Of Endocrnology, vol. 2017. article ID 7454376.

Whitaker Elam, R. (2021, January 20). Osteoporosis. Retrieved from Medscape.com: https://emedicine.medscape.com/article/330598-overview



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