Skeleton Pirate

Skeleton Pirate
Artist: LindaB


Have you experienced, or read about, negative, and even dangerous, side effects from Fosamax (alendronate), Boniva (ibandronate), Actonel (risedronate), and other bisphosphonates prescribed for osteoporosis? If you have, then rest assured there is a safe, effective treatment for this condition. Strontium, primarily in the form of strontium citrate, is taken orally once a day.

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Saturday, September 12, 2015

Fracture Warnings for Invokana and Invokamet Diabetes Drugs

“The US Food and Drug Administration (FDA) has strengthened its warning for canagliflozin (Invokana, Invokamet, Johnson & Johnson/Janssen) related to the increased risk for bone fractures.”

“The …product label for canagliflozin had already mentioned the risk for bone fractures. Now, based on new confirmatory information from several clinical trials, the FDA has added further warning and precaution information. In the trials, the fractures affected the upper extremities, occurred as early as 12 weeks after starting the drug, and typically arose from minor trauma such as falling from a standing height.”

“The FDA has also added new information to the label about decreased bone mineral density at the hip and lower spine.”

“The FDA is also evaluating the possible risk for bone fractures for other drugs in the sodium glucose cotransporter 2 (SGLT2) inhibitor class, including dapagliflozin (Farxiga, Xigduo XR, AstraZeneca) and empagliflozin (Jardiance, Glyxambi, Synjardy, Lilly/Boehringer Ingelheim), to determine whether additional label changes or studies are needed. The label for Farxiga mentions a small number of cases of fractures in patients with renal impairment; the Jardiance prescribing information does not mention bone effects.”

“…SGLT2 inhibitors increase concentrations of phosphate in serum, probably via increased tubular reabsorption, which has the potential to adversely affect bone.”

“Furthermore…SGLT2 inhibitors increase concentrations of parathyroid hormone (PTH). Sustained increases in PTH concentration enhance bone resorption and increase the risk for bone fractures.”

"Although canagliflozin causes a small increase in mean PTH concentration (7.9%), the standard deviation is large. Thus, a substantial number of patients treated with canagliflozin might have a 50% or greater increase in PTH concentrations — a change that could be clinically significant…"

Simeon I. Taylor, MD, professor of medicine at University of Maryland School of Medicine in Baltimore, said, "Although not proven, I believe that increased risk of bone fracture is likely a class effect. Nevertheless, individual drugs differ with respect to selectivity for SGLT2 vs. SGLT1, and also with respect to where on the dose-response curve the approved dose falls. So, it is certainly possible that the magnitude of the risk could vary among individual SGLT2 inhibitors."

Thursday, August 27, 2015

BMD and Strontium Artifact

“The greater increases in BMD are in part due to combined anti-catabolic and bone anabolic effects of strontium ranelate and in part due to the higher atomic number of strontium in bone as compared to calcium. The higher atomic number of strontium (Z = 38) than calcium (Z = 20) leads to greater attenuation of X-rays and consequently an overestimation of BMD as measured by DXA (and expressed as calcium hydroxyapatite equivalent). The greater changes in BMD are clinically useful, allowing the clinician to more easily demonstrate positive changes in BMD as an indication of patient response to therapy. With most osteoporosis therapies, BMD changes in individual patients are likely to fall within the precision error for the densitometer.”

“Although various algorithms for adjusting the bone density in patients on strontium ranelate therapy have been proposed, none are validated. There are likely to be differences in strontium incorporation in bone at different skeletal sites for many reasons. Strontium is preferentially distributed in bone newly formed during strontium ranelate treatment rather than in older bone, formed before treatment initiation. Strontium exchanges more readily on the surface of bone than in deeper bone. It is therefore likely that at different bone sites (trabecular and cortical bone), and with different levels of bone turnover, bone strontium content would be quite variable between individuals. Consequently, adjustment algorithms will not be clinically useful.”

“An adjustment of the lumbar spine BMD was first proposed in the STRATOS study and has been used as an attempt to approximate the increase in BMD related to the pharmacological effect of strontium ranelate. However, this algorithm for adjustment of lumbar spine BMD is complex and based on numerous assumptions.… By the above adjustment algorithm, it is estimated that the BMD overestimation due to strontium in bone accounts for approximately 50% of the measured change in BMD after 3 years of treatment.”

“The increased BMD observed clinically in patients treated with strontium ranelate is both due to the presence of strontium in bone as well as the pharmacological antiresorptive and anabolic activity on bone cells resulting in increased bone tissue with normal bone calcium mineralization. In animal studies, measured-BMD increases correlate with improved bone strength and adjustment of the BMD does not improve the strength-BMD correlation compared with the unadjusted BMD. This indicates that the measured, unadjusted BMD is optimal in predicting improved biomechanical properties in patients on strontium ranelate therapy. The easily discernible BMD increases in strontium ranelate-treated patients will assure the clinician that medication has been ingested, that strontium has been absorbed, and that anti-fracture efficacy in keeping with the results from the pivotal trials can be expected.”

Saturday, August 15, 2015

Histomorphometric and μCT Analysis of Bone Biopsies From Postmenopausal Osteoporotic Women Treated With Strontium Ranelate

“Strontium ranelate is a new anti-osteoporotic treatment. On bone biopsies collected from humans receiving long-term treatment over 5 yr, it has been shown that strontium ranelate has good bone safety and better results than placebo on 3D microarchitecture. Hence, these effects may explain the decreased fracture rate.”

“Introduction: Strontium ranelate's mode of action involving dissociation of bone formation and resorption was shown in preclinical studies and could explain its antifracture efficacy in humans.”

“Materials and Methods: One hundred forty-one transiliac bone biopsies were obtained from 133 postmenopausal osteoporotic women: 49 biopsies after 1–5 yr of 2 g/d strontium ranelate and 92 biopsies at baseline or after 1–5 yr of placebo.”

“Results and Conclusions: Histomorphometry provided a 2D demonstration of the bone safety of strontium ranelate, with significantly higher mineral apposition rate (MAR) in cancellous bone (+9% versus control, p = 0.019) and borderline higher in cortical bone (+10%, p = 0.056). Osteoblast surfaces were significantly higher (+38% versus control, p = 0.047). 3D analysis of 3-yr biopsies with treatment (20 biopsies) and placebo (21 biopsies) using μCT showed significant changes in microarchitecture with, in the strontium ranelate group, higher cortical thickness (+18%, p = 0.008) and trabecular number (+14%, p = 0.05), and lower structure model index (−22%, p = 0.01) and trabecular separation (−16%, p = 0.04), with no change in cortical porosity. The changes in 3D microarchitecture may enhance bone biomechanical competence and explain the decreased fracture rate with strontium ranelate.”

Wandering Skeleton

Wandering Skeleton
Artist: Joel Hoekstra

Osteoporotic Bone

Osteoporotic Bone

How Strontium Builds Bones

Strontium is a mineral that tends to accumulate in bone. Studies have shown that oral doses of strontium are a safe and effective way to prevent and reverse osteoporosis. Doses of 680 mg per day appear to be optimal. See my "For More Information About Strontium" links section.

Osteoporosis is caused by changes in bone production. In healthy young bones there is a constant cycle of new bone growth and bone removal. With age, more bone is removed and less new bone is produced. The bones become less dense and thus more fragile.

Scientists believe that strontium works in two ways. It may stimulate the replication of pre-osteoblasts, leading to an increase in osteoblasts (cells that build bone). Strontium also directly inhibits the activity of osteoclasts (cells that break down bone). The result is stronger bones.

When taking strontium, be sure to take 1200 mg calcium, 1000 IU vitamin D3, and 500 mg magnesium daily. It is best to take strontium late at night on an empty stomach. Calcium and strontium may compete with each other for absorption if taken together.