Strontium and Calcium and Vitamin D

Anyone concerned with bone health, whether taking strontium or not, should have an adequate daily intake of calcium from food or supplements or a combination of the two. In other words, if an individual can get all her calcium from food, she does not need to supplement. However, most people probably will need some calcium supplementation.

The risks of inadequate intake of calcium and vitamin D are reduced calcium absorption, increased serum parathyroid hormone (PTH) concentrations, and bone loss. Low bone mass is a strong predictor of fracture.

There is a rationale for supplementing the diets of elderly subjects with a combination of calcium and vitamin D. Absorption of calcium and possibly of vitamin D and production of vitamin D by the skin decline with aging. Diets deficient in calcium tend also to be deficient in vitamin D because a single food, milk, is the principal dietary source of both these nutrients.

http://www.nejm.org/doi/full/10.1056/NEJM199709043371003#t=article

There is no clinical study of strontium with inadequate calcium and vitamin D because such a study would violate the ethical medical standard of doing no harm to patients.

Before inclusion in the TROPOS study of strontium ranelate, patients were subjected to a run-in study to initiate normalization of their calcium and vitamin D status. The duration of this run-in study was 2 wk to 6 months, depending on the severity of calcium and 25-OH vitamin D (25-OH D) deficiency. All enrolled women received daily supplements of up to 1000 mg of elemental calcium adapted to their needs according to their dietary intake (0, 500, or 1000 mg to reach a total daily intake above 1000 mg), and vitamin D according to their serum 25-OH D levels (800 IU for patients having serum 25-OH D lower than 45 nmol/liter and 400 IU for all the others). For patients with severe vitamin D deficiency (25-OH D lower than 30 nmol/liter) the duration of the run-in period was at least 3 months.

 
https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2004-1774

Combined Strontium and Vitamin D Therapy for Osteoporosis

The following abstract is for a clinical study titled "Correction of Vitamin D Insufficiency with Combined Strontium Ranelate and Vitamin D3 in Osteoporotic Patients" by R. Rizzoli et al. It was made available online 9 December 2013. Please note that I have converted the 25-hydroxyvitamin D units from nmol/l to ng/mL (1 ng/mL = 2.5 nmol/L) and added those units in parentheses. My personal daily osteoporosis therapy includes 2 grams strontium citrate (680 mg strontium) and 1000 IU vitamin D (included in my Nature Made Multi for Him multivitamin).

Objective This study aims to investigate the efficacy and safety of oral fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU daily vs strontium ranelate 2 g daily for correcting vitamin D insufficiency in osteoporosis.

Design A 6-month international, randomized, double-blind, parallel-group, phase 3 study.

Methods A total of 518 men and postmenopausal women aged greater than or equal to 50 years with primary osteoporosis (T-score less than or equal to −2.5 s.d.) and serum 25-hydroxyvitamin D (25(OH)D)greater than 22.5 nmol/l (9 ng/mL) were included. Patients were allocated to strontium ranelate 2 g/vitamin D₃ 1000 IU daily (n=413) or strontium ranelate 2 g daily (n=105). The participants received calcium 1 g daily. The primary endpoint was serum 25(OH)D at last post-baseline evaluation during 3 months.

Results Both groups were comparable at baseline. Mean baseline of 25(OH)D was 44.1 plus or minus 14.6 nmol/l (17.6 ng/mL plus or minus 5.8 ng/mL). After 3 months, the percentage of patients with 25(OH)D greater than or equal to 50 nmol/l (20 ng/mL) was higher with strontium ranelate/vitamin D₃ vs strontium ranelate (84 vs 44%, P less than 0.001; adjusted between-group odds ratio=6.7; 95% CI, 4.2–10.9). The efficacy of the fixed-dose combination on 25(OH)D was maintained at 6 months (86 vs 40%, P less than 0.001). Mean 25(OH)D was 65.1nmol/l (26 ng/mL) and 49.5 nmol/l (19.8 ng/mL), respectively, after 3 months and 66.9 nmol/l (26.8 ng/mL) and 45.4 nmol/l (18.2 ng/mL) after 6 months. Physical performance improved in both groups. Falls were 17 and 20% in the strontium ranelate/vitamin D₃ and strontium ranelate groups respectively. Parathyroid hormone levels were inversely correlated with 25(OH)D. No clinically relevant differences in safety were observed.

Conclusions This study confirms the efficacy and safety of fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU for correction of vitamin D insufficiency in osteoporotic patients. 

http://www.eje-online.org/content/170/3/441.short

Strontium Ranelate Withdrawal from European Countries

Cessation of marketing of Protelos/Osseor: Extract of the letter sent to European Medicine Agency (EMA) and national European Agencies on 10 February 2017

14/03/2017

Similar letters, adapted to local regulations, have been sent to all countries worldwide where Protelos/Osseor® is marketed

PROTELOS/OSSEOR® - Cessation of marketing

On 21 September 2004, Protelos/Osseor^® (strontium ranelate), centrally authorised medicinal product, was granted a Marketing Authorisation by the European Commission for the European Union (EU).

Protelos/Osseor^® is indicated in the treatment of severe osteoporosis in postmenopausal women and in adult men at high risk of fracture, for whom treatment with other medicinal products approved for the treatment of osteoporosis is not possible due to, for example, contraindications or intolerance.

Les Laboratoires Servier hereby notify the cease of the marketing, permanently, in the European countries where it is currently marketed.
This worldwide and strategic decision is taken for commercial reasons based on the following grounds:

• The restricted indication/limited use of Protelos/Osseor®,
• The continuous decrease of patients treated with Protelos/Osseor®.

Les Laboratoires Servier will cease the distribution of Protelos/Osseor® in August 2017.

Servier, founded in 1954, is the first independent pharmaceutical group. We are present in 140 countries, with more than 21 000 employees, including close to 3000 in R&D.

http://www.servier.com/content/cessation-marketing-protelososseor-extract-letter-sent-european-medicine-agency-ema-and

My note: Those who will no longer be prescribed strontium ranelate can buy nonprescription strontium citrate. 

MOTS and COMB Study Comparison

A one-year study on strontium citrate combined with melatonin and other supplements and named the Melatonin-micronutrients Osteopenia Treatment Study (MOTS) was recently published (January 26, 2017). I’d like to compare it to the Combination of Micronutrients for Bone (COMB) Study published in 2012. See the following chart:

        
    COMB Study                                                               MOTS

Study size                        114                                                                                  20

Baseline BMD status      osteoporosis                                                                   osteopenia

Strontium (citrate)               680 mg                                                                          450 mg

Vitamin K2 (MK7)               100 mcg                                                                         60 mcg

Melatonin                              none                                                                                5 mg                        

Vitamin D3                         2000 IU                                                                          2000 IU

Docosahexanoic acid (DHA)   250 mg                                                                      none

Magnesium                             25 mg                                                                          none

Lumbar spine BMD             6% increase                                                             4.3% increase

Femoral neck BMD             4% increase                                                             2.2% increase

Total hip BMD               3% increase                                                             No sign. diff., pos. trend

I could have predicted the results on BMD. How? Well, it had previously been shown, from studies on strontium ranelate, that strontium increased BMD at all dosages studied, but the optimum increases were gained with 680 mg strontium. Also, melatonin has been used for years as a sleep aid, but there is little evidence for it as a bone supplement. The authors of MOTS named two studies on melatonin listed below.         

“Limitations to this study include low number of subjects, lack of a diverse cohort and lack of different micronutrient combinations on primary and secondary endpoints in MOTS clinical trial.”

Despite the limitations of MOTS, there is valuable information to be gained from it:

MOTS increased awareness of the importance of preventative care in patients with osteopenia. “Over half of all women in the U.S. above age 50 have osteopenia with a prevalence of approximately 3.4 times more than osteoporosis. Consequently, twice the number of fractures arises from women with osteopenia as they represent almost 50% of the total population at risk.”

“The 10-year vertebral fracture risk probability decreased by 6.48% in response to MSDK (melatonin, strontium, vitamins D and K) therapy compared to 10.8% increase in placebo.”

“MSDK reduced bone marker turnover primarily by increasing the bone formation marker P1NP and maintaining healthy bone turnover.”

“MSDK demonstrated positive effects on inflammatory status and improved quality of life especially related to sleep.”

MOTS confirmed that dosages lower than 680 mg strontium will increase BMD by lower percentages.

                       

http://strontiumforbones.blogspot.com/2012/02/combination-of-micronutrients-for-bone.html

https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/vmFJfarchkyMAtwWn.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310667/

https://clinicaltrials.gov/ct2/show/NCT01870115?term=strontium+citrate&rank=1

Kotlarczyk MP, Lassila HC, O’Neil CK, D’Amico F, Enderby LT, Witt‐Enderby PA, Balk JL. Melatonin osteoporosis prevention study (MOPS): a randomized, double‐blind, placebo‐controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women. J Pineal Res. 2012; 52:414–26. doi: 10.1111/j.1600‐079X.2011.00956.x

Amstrup AK, Sikjaer T, Heickendorff L, Mosekilde L, Rejnmark L. Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial. J Pineal Res. 2015; 59:221–29. doi:10.1111/jpi.12252