Strontium Boost by AlgaeCal International

EFFECTIVE

• Dental hypersensitivity. Topical use of strontium acetate 8% and strontium chloride 10% in toothpaste relieves the pain of sensitive teeth (11745,11746,32177,76519,76570,76590). Best results are obtained with twice daily brushing (11756,32177,76590).
• Painful bony metastases. Intravenous administration of strontium-89 chloride is effective for metastatic bone pain (11749,11750,11751,11752,76608).

LIKELY EFFECTIVE

• Osteoporosis. Many clinical trials and a meta-analysis have been conducted in postmenopausal women with osteoporosis. Taking strontium ranelate orally appears to reduce the risk of vertebral fractures by 40% in postmenopausal women with osteoporosis and a history of vertebral fracture. There is some evidence that it might actually increase bone mineral density (BMD) in these patients by 14% at the lumbar spine and 8% at the femoral neck. Taking strontium ranelate orally also appears to reduce the risk of nonvertebral fractures by 31% in postmenopausal women with osteoporosis (11392,11393,11395,76597,94010). In patients with or without a history of vertebral fracture, taking strontium ranelate orally for up to 10 years also reduces the risk of nonvertebral fractures by 15% to 38% and vertebral fractures by 24% to 35%. BMD at the lumbar spine, femoral neck, and total hip also continued to increase over 5 years (76527,76562,94012). In postmenopausal women over the age of 80 years, taking strontium ranelate 2 grams orally daily for 4 years reduces the relative risk of vertebral fractures by 31%, nonvertebral fractures by 33%, major nonvertebral fractures by 27%, and hip fractures by 24% compared to placebo (94011). Some preliminary clinical research also shows that taking strontium ranelate for 2 years significantly increases lumbar spine, femoral neck, and total hip BMD compared to placebo in men with osteoporosis (94002). There is conflicting evidence about the efficacy of strontium ranelate in patients previously treated with bisphosphonates. Preliminary evidence in postmenopausal women with osteoporosis suggests that prior treatment with bisphosphonate therapy might blunt the BMD response in patients taking strontium ranelate 2 grams daily for 2 years. In bisphosphonate naïve patients, treatment with strontium lead to increases in BMD at the spine, hip, and heel. In patients with prior bisphosphonate therapy, treatment with strontium lead to increases in BMD at the spine and hip, but not the heel. (94009). Based on the benefits of strontium ranelate on BMD and fracture risk, it was approved in Europe in 2004 for the treatment of severe osteoporosis in postmenopausal women, and later granted market authorization for men with osteoporosis. However, its use is associated with cardiac events and thromboembolism; it is therefore contraindicated in patients with a history or risk of venous thromboembolism, uncontrolled hypertension, ischemic heart disease, peripheral heart disease, and/or cerebrovascular disease. Because of its limited use in patients with osteoporosis, the manufacturers of prescription strontium ranelate (Protelos) discontinued its manufacturing in August 2017 (95698). Strontium ranelate is not approved for use in the US.

POSSIBLY EFFECTIVE

• Osteoarthritis. Taking strontium ranelate orally for 3 years appears to improve back pain and reduce the risk of spinal osteoarthritis progression by 42% in postmenopausal women with a history of vertebral fracture (76558). In patients with knee osteoarthritis, taking strontium ranelate 1-2 grams daily for 3 years reduces joint space narrowing by 0.1-0.14 mm and improves overall symptoms and pain symptoms, and may improve stiffness and physical function (94006,94007). The dose of 2 grams daily seems to be more effective than a lower dose of 1 gram daily (94007,94008).
• Prostate cancer. Intravenous administration of strontium-89 chloride seems to slow the progression of treatment-resistant prostate cancer and to relieve pain (11747,11748).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Fractures. Preliminary clinical research in patients over 60 with a wrist fracture shows that taking strontium ranelate 2 grams daily for 3 months, in addition to calcium and vitamin D, does not improve nor accelerate wrist fracture healing compared to calcium and vitamin D alone (94005).
• Pruritus. Topical administration of a product containing strontium chloride 4% (TriCalm, Cosmederm Bioscience) 15 minutes prior to itch induction with cowhage, seems to reduce itch intensity and duration when compared with placebo. It also seems to decrease itch intensity more than topical hydrocortisone 1% or diphenhydramine 2% (94004). More evidence is needed to rate strontium for these uses.

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LIKELY SAFE ...when consumed orally in food amounts. Strontium has not been linked to toxicity when consumed in dietary amounts, which are typically about 0.5-1.5 mg daily (14554,14560). ...when strontium-89 chloride is used intravenously and appropriately. Strontium-89 chloride is an FDA-approved product (4948). ...when strontium chloride is used topically and appropriately as a toothpaste. Strontium chloride hexahydrate (Sensodyne-SC) is an FDA-approved product (9).

POSSIBLY SAFE ...when strontium ranelate is used orally and appropriately. Strontium ranelate 2 grams daily, providing elemental strontium 680 mg daily, seems to be safe when used for up to 10 years (11392,11393,11395,14549,94012).

POSSIBLY UNSAFE ...when used orally in high doses. Very high doses may adversely affect bone structure, although data in humans is limited (11394,11399,14554,14556). Until more is known, advise patients to avoid doses of elemental strontium above 680 mg/day. There is insufficient reliable information available about the safety of strontium chloride, the form most commonly used in dietary supplements, when used orally.

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed orally in food amounts. Strontium has not been linked to toxicity when consumed in dietary amounts, which are typically about 0.5 mg to 1.5 mg/day (14554,14560). ...when strontium chloride is used topically and appropriately as a toothpaste (9). Strontium chloride hexahydrate (Sensodyne-SC) is an FDA approved product.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when strontium-89 chloride is used during pregnancy or lactation. Strontium-89 chloride is a radioactive isotope which may cause fetal harm. It is FDA pregnancy risk category D; avoid using (11755). Since strontium behaves similarly to calcium in the body, strontium-89 is likely to be excreted into breast milk; avoid using during lactation (11755). There is insufficient reliable information about the safety of oral strontium when used in amounts exceeding typical dietary intake during pregnancy or lactation; avoid using.

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ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Preliminary research suggests that treatment with estrogens for 5-6 weeks might decrease urinary strontium excretion (11405). The clinical significance of this is unknown.  Details Some examples of estrogens include estradiol, ethinyl estradiol, conjugated equine estrogens (Premarin), and others.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Strontium is a divalent cation with similar properties to calcium. It is likely to form complexes with quinolones in the gastrointestinal (GI) tract, preventing absorption of the antibiotic (14549). Recommend taking strontium supplements at least 2 hours before or after quinolones to avoid an interaction.  Details Quinolone antibiotics include ciprofloxacin (Cipro), gemifloxacin (Factive), levofloxacin, moxifloxacin (Avelox), and others.

TETRACYCLINE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Strontium is a divalent cation with similar properties to calcium. It is likely to form complexes with tetracyclines in the gastrointestinal (GI) tract, preventing absorption of the antibiotic (14549). Recommend taking strontium supplements at least 2 hours before or after tetracyclines to avoid an interaction.  Details Tetracycline antibiotics include demeclocycline (Declomycin), doxycycline (Vibramycin), minocycline (Minocin), and tetracycline.

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General ...Orally, strontium ranelate seems to be well tolerated when used in doses up to 2 grams daily, providing 680 mg of elemental strontium daily, and taken for up to 10 years. Common side effects, which are usually mild and transient, can include nausea, diarrhea, headache, dermatitis, and eczema (11392,11393,11395,14549). Occasionally, altered consciousness, memory loss, and seizures have been reported (14549). In clinical trials, strontium ranelate seems to increase the relative risk of venous thromboembolism and pulmonary embolism by about 50% compared with placebo (14561,14562). The reason for this is unknown. Strontium ranelate also seems to increase the risk of myocardial infarction by about 1.6-fold in patients with osteoporosis (95699).
There is some concern that doses of strontium higher than those used in clinical trials may adversely affect bone by impairing mineralization and reducing calcium absorption, leading to abnormal skeletal development and reduced bone quality (11394,11399,14554,14557). This would manifest as rickets if it occurs during bone growth, and as osteomalacia after growth is complete (14556). The concern is mainly based on animal data, although strontium-related rickets has been observed in children eating plant-derived foods grown in locations with high soil strontium levels (11399,14554,14556,14557). Accumulation of strontium has also been reported in people with end-stage renal disease, especially those on dialysis, and has been linked to osteomalacia in such patients. Elevated serum and bone strontium levels seem to occur more commonly in patients with osteomalacia than in those with other types of renal osteodystrophy or no bone changes. Strontium is thought to accumulate due to reduced renal excretion and also the presence of strontium in dialysis fluids (14554,14555,14557,14559). Intravenously, strontium-89 can cause a transient increase in bone pain 36-72 hours after injection (11755). It also causes bone marrow toxicity, particularly affecting platelet and white blood cell counts (11755).

Cardiovascular ...Orally, clinical research shows that strontium ranelate increases the relative risk of venous thromboembolism and pulmonary embolism by about 50% compared with placebo (14561,14562). The reason for this is unknown. Strontium ranelate also seems to increase the risk of myocardial infarction by about 1.6-fold in patients with osteoporosis (95699).

Dermatologic ...Orally, common side effects of strontium ranelate can include dermatitis and eczema (11392,11393,11395,14549).

Gastrointestinal ...Orally, strontium ranelate can cause stomach pain, diarrhea, and nausea, particularly at higher doses (14561,76541,94010,94012).

Hematologic ...Intravenously, strontium-89 causes bone marrow toxicity, particularly affecting platelet and white blood cell counts. Platelet levels fall by about 30% and the nadir is generally 12 to 16 weeks after injection. The effect on white blood cells is variable. Blood cell counts generally recover slowly over a period of about 6 months (11752,11755).

Musculoskeletal ...There is some concern that doses of strontium higher than those used in clinical trials may adversely affect bone by impairing mineralization and reducing calcium absorption, leading to abnormal skeletal development and reduced bone quality (11394,11399,14554,14557). This would manifest as rickets if it occurs during bone growth, and as osteomalacia after growth is complete (14556). The concern is mainly based on animal data, although strontium-related rickets has been observed in children eating plant-derived foods grown in locations with high soil strontium levels (>350 ppm), especially if they also have inadequate protein, calcium, and vitamin D intake (11399,14554,14556,14557). Accumulation of strontium has also been reported in people with end-stage renal disease, especially those on dialysis, and has been linked to osteomalacia in such patients. Elevated serum and bone strontium levels seem to occur more commonly in patients with osteomalacia than in those with other types of renal osteodystrophy or no bone changes. Strontium is thought to accumulate due to reduced renal excretion and also the presence of strontium in dialysis fluids (14554,14555,14557,14559).

Neurologic/CNS ...Orally, strontium ranelate has reportedly caused altered consciousness, memory loss, and seizures on occasion (14549).

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