Treatment of Osteoporosis with Oral Strontium Citrate

Introduction

Osteoporosis is a complex medical condition that results in  thinning and weakening of  bone. Osteoporosis may be defined empirically as the decrease in   bone mass density, relative to normal values, at a particular age in life.  Resulting in weaker bone, the patient with osteoporosis will have a weakened skeletal system resulting in bone structure that has a  higher risk of fracture This problem of the bone relates to the structural inability to adequately support body weight.  Osteoporosis is a systemic skeletal disease characterized by decreased bone mass, weakened bone tissue leading to increased risk of bone fractures.  Women can lose up to 20 percent of their bone mass in the five to seven years following menopause, making them more susceptible to osteoporosis.

Disease severity is defined by the World Health Organization (WHO) by an individual’s bone mineral density (BMD) compared to mean peak young-adult BMD.  Bone mass which is less than 1 standard deviation (SD) from the mean is considered osteopenia, while BMD less than 2.5 SD from the mean is diagnostic for osteoporosis, noting that osteoporosis implies the subject bone is normal in every other aspect, vis a vis  osteomalacia, a metabolic disorder resulting in faulty mineral deposition in bone.

Osteoporosis can be divided into two arbitrary categories.

  1. Type I osteoporosis occurs in post-menopausal women, and is due to estrogen deficiency.
  2. Type II osteoporosis occurs in both men and women (about two times more frequently in women), and is due to aging, and calcium deficiency over many years.

Both men and women achieve their “peak bone mass, ” that is, greatest bone density, during  the third decade of life. Bone mass then  steadily decreases with age. Rates of bone density decrease increase in  pregnant and lactating women, as the  rate of bone loss will temporarily increase due to the increased calcium demands of pregnancy or breastfeeding.  These effects may be mitigated by the administration of  increased dietary intake of calcium.

Osteoporosis is a disease in which bones become fragile and become more likely to break (fracture). If not prevented or if left untreated, osteoporosis can progress painlessly until a bone crushes or breaks. These fractures occur most commonly  in the hip, spine, and wrist. Any bone can be affected, but of fractures of the spine and hip are of greatest concern. Women are 4 times more likely to develop osteoporosis than are men.

In the U.S., 10 million individuals already have this disease. Almost 34 million more are estimated to have low bone mass (density), thereby placing them at increased risk.  Eighty percent of those with osteoporosis are women. Of people older than 50 years, 1 in 2 women and 1 in 8 men are predicted to have an osteoporosis-related fracture in their lifetime.  The prevalence of osteoporosis among post menopausal  white women is 14% in those aged 50-59 years, 22% in those aged 60-69 years, 39% in those aged 70-79 years, and 70% in those aged 80 years and older. Significant risk has been reported in people of all ethnic backgrounds, white and Asian racial groups at a somewhat increased risk.

Osteoporosis develops asymptomatically, the first clinical sign  can be a sudden back pain resulting from an otherwise minor trauma.  After sudden movement, strain, bump, accident or fall  a vertebrum may fracture or  collapse. It is the wedge shaped compression fracture of the spine that causes the commonly seen spinal deformities, known as ‘Dowager’s Hump,’ kyphosis or stooped posture.

  Risk Factors of Osteoporosis

  • History of fracture after age 50
  • Low bone mass (density).
  • History of fracture in a close relative
  • Females are at greater risk than males.
  • Thin/ small frame
  • Risk increases with age.
  • Positive family history for osteoporosis.
  • Estrogen deficiency.
    •  Menopause.
    • Total hysterectomy.
  • Abnormal absence of menstrual periods (amenorrhea).
  • Eating disorders including Anorexia Nervosa.
  • Low dietary calcium intake.
  • Vitamin D deficiency.
  • Use of certain medications (corticosteroids, chemotherapy, anticonvulsants, diuretics and others)
  • Low testosterone levels in men and women.
  • An inactive lifestyle.
  • Current cigarette smoking.
  • Excessive use of alcohol.
  • Caucasian and  Asians are at the greatest risk,  although African Americans and Hispanic Americans are at significant risk as well.

Elemental Strontium

Strontium is a naturally occuring element that forms an important function in the formation and maintenance of bone matrix.  Strontium wasting can be observed in otherwise healthy individuals.  Hair analysis can be performed in persons with osteoporosis or in those persons at risk for the development of osteoporosis, and elevated levels of strontium will be detected. As with many other ‘trace minerals,’ strontium is, or should be found in our grain.  As the fields are cropped repeatedly, strontium, along with zinc, selenium, vanadium, chromium, boron, and the like, are gradually depleted.  Replacement of this inexpensive element into our diet can arrest the progression of osteoporosis, and in many persons, actually reverse a good bit of the damage.

Strontium is element number 38 of the periodic table of elements. It was discovered in 1808 and was named after Strontian, a town in Scotland. Strontium is one of the most abundant elements on earth, comprising about 0.04 percent of the earth’s crust. At a concentration of 400 parts per million, there is more strontium in the earth’s crust than carbon. Strontium is also the most abundant trace element in seawater, at a concentration of 8.1 parts per million. The human body contains about 320 mg of strontium, nearly all of which is in bone and connective tissue.

Because of its chemical similarity to calcium, strontium can replace calcium to some extent in various biochemical processes in the body, including replacing a small proportion of the calcium in hydroxyapatite crystals of calcified tissues such as bones and teeth. Strontium in these crystals imparts additional strength to these tissues. Strontium also appears to draw extra calcium into bones. When rats or guinea pigs are fed increased amounts of strontium, their bones and teeth became thicker and stronger.

Treatment of Osteoporosis with Strontium

In vitro, strontium ranelate has anabolic and anti-resorptive activity in bone, thereby  increasing collagen and non-collagen protein synthesis, enhancing pre-osteoblast differentiation, inhibiting osteoclast differentiation, and reducing osteoclast function. Strontium ranelate was shown to enhance pre-osteoblastic cell replication and collagen synthesis in culture without affecting bone mineralization. Studies performed in healthy animals have shown that strontium ranelate not only increases bone mass at various skeletal sites but also improves mechanical properties of femoral, humeral and vertebral bones.

The increase in bone density is closely correlated with increases in biomechanical bone strength. Reductions in vertebral fracture were seen in patients with and without prevalent vertebral fracture. Nonvertebral fractures were also significantly reduced. In a subgroup of patients at high risk for hip fracture, there was a significant reduction in hip fracture risk. Strontium ranelate is well tolerated with nausea, diarrhea, headache, and dermatitis more frequent in treated patients only for the first 3 months of therapy. These data suggest that strontium ranelate is a well-tolerated and effective therapy to treat osteoporosis in the postmenopausal patient,  reducing vertebral and nonvertebral fracture by a novel dual antiresorptive and anabolic action on bone.

Strontium Renelate is currently available in Europe for the treatment of osteoporosis.  The renelate salt is being widely used instead of the bisphonates, mentioned below.  Found to be twice as effective as Fosamax and Actonel, Strontium will actually reverse many of the effects of osteoporosis.

Based on the studies showing that strontium improves bone density in osteoporosis, scientists at the Bone and Cartilage Metabolism Research Unit, University Hospital, Liege, Belgium, hypothesized that strontium might also improve cartilage metabolism in osteoarthritis (OA).8 They performed an in vitro investigation using cartilage-forming cells (chondrocytes) obtained from normal adults and patients with osteoarthritis. Chondrocytes were cultured for 24 to 72 hours with strontium, and Proteoglycan (PG) content was determined—i.e., structural components of cartilage, including hyaluronic acid, glucosamine and chondroitin sulfate. These substances—Proteoglycans, also known as Glycosaminoglycans—are known to decline dramatically with age9 (Fig. 2). The researchers found that strontium strongly stimulated PG production. This suggests a cartilage-growth-promoting effect of strontium, and provides a sound basis for clinical testing of strontium in osteo- and other forms of arthritis.

In a European study, strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A highly significant reduction in  vertebral fracture risk was demonstrated. These vertebral fractures were reduced by 40%  after 3 years, independent of age, initial BMD.

Strontium ranelate is a patented strontium salt, currently available in Europe.  We pooled data of two large multinational randomized double-blind studies with a population of 5082 (2536 receiving strontium ranelate 2 g/day and 2546 receiving a placebo), 74 years of age on average, and a 3-year follow-up. The treatment decreased the risk of both vertebral (relative risk = 0.60 [0.53-0.69] p < 0.001) and nonvertebral (RR = 0.85 [0.74-0.99] p = 0.03) fractures. The decrease in risk of vertebral fractures was 37% (p = 0.003) in women or = 80 years. The RR of vertebral fracture was 0.28 (0.07-0.99) in osteopenic and 0.61 (0.53-0.70). In 2605 patients, the risk of experiencing a first vertebral fracture was reduced by 48% (p < 0.001). The risk of experiencing a second vertebral fracture was reduced by 45% (p < 0.001; 1100 patients). Moreover, the risk of experiencing more than two vertebral fractures was reduced by 33% (p < 0.001; 1365 patients). This study shows that a 3-year treatment with strontium ranelate leads to antivertebral fracture efficacy in postmenopausal women independently of baseline osteoporotic risk factors.(6)

Its effects on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated osteoclast, preincubation of bone slices with strontium ranelate-induced dose-dependent inhibition of the bone-resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. Its effect in postmenopausal women with established osteoporosis was assessed during an international, prospective, double-blind, randomized, placebo-controlled phase 3 program comparing strontium ranelate 2 g daily with placebo. The 3-year analysis of the phase 3 study, Spinal Osteoporosis Therapeutic Intervention, evaluating the effect of strontium ranelate 2 g/day on vertebral fracture rates, revealed a significant 41% reduction in the relative risk of patients experiencing new vertebral fracture with strontium ranelate over 3 years. A second phase 3 study showed a significant reduction in the relative risk of experiencing a nonvertebral fracture in the group treated with strontium ranelate over 3 years. These results show that strontium ranelate is a new, effective, and safe treatment for vertebral and hip osteoporosis, with a unique mode of action, increasing bone formation and decreasing bone resorption leading to a rebalance of bone turnover in favor of bone formation.

Availability and Cost of Strontium Citrate

While the renelate salt is not yet available in the United States, strontium is currently available in the form of a citrate salt.  The citrate salt may offer advantages over the renelate salt in that the citrate moiety is not ‘new to nature,’ and the citrate moiety may be useful in and of itself as an anti-oxidant agent.

Strontium Citrate is available in the United States in an over-the counter form. Costing as little as $18/month, this treatment of osteoporosis is considerably more affordable than Fosamax and Actonel, and is considerably more effective.  The only noticable side-effect is some minor upset stomach that occurs if the product is taken on an empty stomach.  Strontium Citrate can be taken in lieu of the bisphonates, and supplemental dietary calcium can be reduced.  Strontium should not be taken at the same time of day as one takes calcium, in that these minerals compete for absorbance in the GI tract.

Strontium to Treat Dental Cavities

Strontium also has been shown to reduce the incidence of cavities. In a 10-year study, the United States Navy Dental Service examined the teeth of about 270,000 naval recruits. Of those, only 360 were found to be completely free of cavities. Curiously, 10 percent of those 360 individuals came from a small area around Rossburg, Ohio, where the water contains unusually high concentrations of strontium. Epidemiologic studies have shown that strontium concentrations of 6 to 10 mg/liter in the water supply are associated with a reduced incidence of cavities. Administering these levels of strontium also reduced the incidence of cavities in animal studies.

Other Treatment Options in Osteoporosis

There are several available medications used for osteoporosis treatment. These include:

  1. Bisphosphanates (e.g. Fosamax, Actonel) are chemicals that inhibit bone breakdown through dysregulation of a cellular system involved in the breakdown of bone. This bone turnover, or replacement of old bone with new bone, is a normal process within our body. If patients with osteoporosis replace less new bone as the old bone is broken down, bone mass decreases. Bisphosphanates slow the rate of bone breakdown to help maintain bone mass by inhibiting the osteoclast, the cell line responsible for bone breakdown.
  1. Calcitonin (Miacalcin) is a naturally occurring hormone that can be given as an injection or taken as a nasal spray. Calcitonin inhibits the function of the cells that breakdown bone, the osteoclasts. The nasal spray has greatly improved the use of calcitonin, and it is much more commonly used today. Calcitonin has been shown to slow bone loss, and also decrease pain associated with osteoporosis fractures.
  1. Raloxifene is a newer medication that has been developed to provide some of the same advantages of estrogen (HRT), without the potential side-effects. Raloxifene is a type of medication called a Selective Estrogen Receptor Modulator, or SERM. The effects of Raloxifene have been shown to be similar to estrogen, including an increase in bone mass and lower cholesterol. However, the SERMs do not have the same effects on the uterine lining, and therefore do not need to be combined with a progesterone. Furthermore, there is evidence that Raloxifene may decrease the risk of breast cancer.

Estrogen 4.  Hormonal replacement therapy, or HRT, not only helps maintain, but it can increase bone mass after menopause. Multiple studies have shown the benefits of estrogen therapy, including a lower risk of osteoporosis and fractured bones. In addition, other benefits of estrogen replacement in the postmenopausal patient include lower cholesterol, decreased risk of colon cancer, and fewer postmenopausal symptoms.

HRT was shown to increase the risk of uterine cancer, but this risk is eliminated when the estrogen is combined with progesterone. There have been studies showing an increase risk of breast cancer in some study populations. Patients on HRT have also shown a slightly increased risk of developing blood clots and strokes.

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References

  1. Khan AW, Khan A: Anabolic agents: a new chapter in the management of osteoporosis. J Obstet Gynaecol Can. 2006 Mar;28(3):136-41.
  2. Jupsin I, Collette J, Henrotin Y, et al: Strontium ranelate. Curr Opin Investig Drugs.  Apr;6(4):435-44, 2005. 3. Fernandez-Garcia D, Alonso G, Munoz-Torres M:  Anabolic therapy of osteoporosis. Med Clin (Barc). 2005 Sep 17;125(9):341-5. 4.  Marie PJ. Strontium as therapy for osteoporosis. Curr Opin Pharmacol. Sept 2005.
  3. Reginster JY, Sarlet N, Lejeune E, Leonori L:  Strontium ranelate: a new treatment for postmenopausal osteoporosis with a dual mode of action.Curr Osteoporos Rep. Mar;3(1):30-4, 2005.
  4. Roux C, Reginster JY, Fechtenbaum J, et al: Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors.  J Bone Miner Res. 2006 Apr;21(4):536-42. Epub 2006 Apr 5.
  5. Marie, P.J., and Hott, M. Short-term effects of fluoride and strontium on bone formation and resorption in the mouse. Metabolism, 1986, 35:547-551.
  6. Marie, P.J., Skoryna, S.C., Pivon, R.J., et al: Histomorphometry of bone changes in stable strontium therapy. In: Trace substances in environmental health XIX, edited by D.D. Hemphill, University of Missouri, Columbia, Missouri, 1985, 193-208.
  7. Meunier, P.J., Slosman, D.O., Delmas, P.D., et al: Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis—a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab, May 2002; 87(5):2060-6.
  8. Meunier, P.J., Roux, C., Seeman, E., et al: The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis, N Engl J Med, 2004, Jan 29;350(5):459-68.
  9. Skoryna, S.C., 1981. Effects of oral supplementation with stable strontium. Can Med Assoc J, 125: 703-712.
  10. Gaby, A.R. Preventing and Reversing Osteoporosis, Prima Publishing, Rocklin, CA, 1994.
  11. Henrotin Y., Labasse A., Zheng S.X., et al: Strontium ranelate increases cartilage matrix formation. J Bone Miner Res, 2001, Feb; 16(2):299-308.
  12. Hall, D.A. The Ageing of Connective Tissue, Academic Press, San Francisco, 1976.
  13. Reginster, J.Y., Deroisy, R., Dougados, M., et al: Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year, double-masked, dose-ranging, placebo-controlled PREVOS trial. Osteoporos Int, 2002, Dec;13(12): 925-31.
  14. Simon LS.  Osteoporosis. Clin Geriatr Med.  Aug;21(3):603-29, viii.,2005.
  15. McCaslin, F.E., Jr., and Janes, J.M. The effect of strontium lactate in the treatment of osteoporosis. Proc Staff Meetings Mayo Clin, 1959, 34:329-334.

David S Klein, MD

David S. Klein, MD, FACA, FACPM was born in Washington, DC, and was raised in Chevy Chase, Maryland. He completed his undergraduate education at the University of Maryland with degrees in Chemistry and Psychology. Medical School was completed at the University of Maryland at Baltimore, followed by Internship in General Surgery at the University of North Carolina and Residency in Anesthesiology at the Duke University, Durham, North Carolina. Dr Klein has been practicing medicine since 1983, concentrating in Pain Medicine, Minimally Invasive Medicine and Surgery, and Neuroendocrinology. Earning Board Certification in Anesthesiology, Dr. Klein was elected Fellow in the American College of Anesthesiology, and he was elected Fellow in the American College of Pain Medicine. He is currently an adjunct Associate Professor at the University of Central Florida, School of Medicine. He has focused his private practice on treating patients with hormone imbalance issues, nutritional deficiency related medical problems as well as pain related issues and impairment. With a highly-complex, CLIA licensed laboratory in-house, he has been able to provide rapid-turn around analysis efficiently and cost-effectively. Lecturing extensively nationally as well as internationally, Dr. Klein has authored many articles on topics relating to pain, injury and nutritionally modulated illness. His radio show, “Pain Free Living,” received top ratings during the 6 years it was on the air. Currently practicing in Longwood, Florida, Dr. Klein practices entirely in the office setting.

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