A new study has shown that an infusion of the bisphosphonate Reclast (zoledronate), prescribed as a stand-alone osteoporosis treatment and to offset the rapid bone loss that occurs after stopping treatment with Prolia (denosumab), doesn’t help to preserve bone mineral density. Savers know that osteoporosis drugs are neither effective nor safe, yet doctors continue to prescribe them in spite of studies like the one we’ll review today.
Meanwhile, Big Pharma is in the process of developing an osteoarthritis drug with the mechanism of action of a failed experimental osteoporosis drug that had to be dropped due to its dangerous side effects.
And last but not least, this month’s Bulletin ends on a high note. A British study has found that as little as one to two minutes of medium-to-high intensity exercise on a daily basis improves bone health. It’s a powerful testament that if we provide our bones with what they need, they will thrive.
New Study: Zolendronate Infusion Fails To Halt Bone Loss
A case study has shed light on the ineffectiveness of the popular bisphosphonate zoledronate, also known as zoledronic acid and marketed as Reclast in the U.S. and Aclasta in Europe. In addition to its usual application as a yearly infusion, it is also often prescribed to women at the end of treatment with Prolia, (denosumab).
When denosumab treatment is discontinued, bone resorption (which was previously being blocked by the drug) rapidly picks back up and reaches twice its normal rate within a year of the last injection. Stopping the drug treatment results in a drastic drop in bone mineral density (BMD) and an increase in fracture risk.1 To address this problem, doctors often prescribe one infusion of zoledronate.
The report, published in the Medical Journal Calcified Tissue International, followed women with the goal of establishing whether zoledronate is an effective means of preventing bone loss after the discontinuation of long-term treatment with denosumab.
“The six women, who had received continuous denosumab for seven years, had substantial gains in bone mineral density (BMD) — increasing 18.5% in the spine and 6.9% in total hip. The patients were given a single infusion of zoledronate (5 mg) six months after the last dose of denosumab. Post-zoledronate BMDs were measured 18-23 months after treatment. The findings:
There were significant BMD declines at each site (Pspine = 0.043, Phip = 0.005).
Spine BMD remained significantly above the pre-denosumab baseline (+9.3%, P = 0.003), but hip BMD was not significantly different from baseline (?2.9%).
Serum P1NP levels were between 39 and 60 ?g/L (mean 52 ?g/L), suggesting that the zoledronate treatment had insufficiently inhibited bone turnover.
The authors conclude that administration of a single infusion of zoledronate six months after the last dose of denosumab is not sufficient to preserve the BMD gains that result from long-term denosumab treatment.”1
In spite of this clear evidence that these drugs don’t work, doctors continue to prescribe them. Anti-resorptive drugs, which include bisphosphonates, don’t work for a very simple reason: they disrupt the natural bone remodeling process, preventing your body from safely replacing old bone with newer, stronger bone. When your body can’t remove damaged bone due to these drugs, it piles up new bone over the old, creating denser– but more brittle– bones, which are more prone to fracture.
It’s no wonder that when treatment with Prolia is stopped, osteoclasts work hard to remove the damaged bone it was forced to leave behind. Taking a second drug to prevent that response creates the same problems, but with a whole new swath of side effects.
This is yet more proof that a drug-free osteoporosis treatment is the safest and most effective way to increase the density, quality, and strength of your bones without the laundry list of awful side effects, the disappointment, and expense of a failed course of pharmaceutical treatment.
Experimental Osteoarthritis Drug Mimics Merck’s Failed Osteoporosis Medication Odanacatib
Medivir AB, a European pharmaceutical company, has reported that test results show that an experimental osteoarthritis drug doesn’t have the pain-relieving effect they were hoping to establish. However, they found that the drug slowed the thinning of bone area and cartilage in the knees of patients. They claim that this data demonstrates that the drug, called MIV-711, could be the first disease-modifying drug for osteoarthritis.2
This experimental drug has the same mechanism of action as Merck’s failed osteoporosis drug odanacatib, which we have previously written about. During Phase III trials, odanacatib, a cathepsin K inhibitor, increased the risk of atrial fibrillation and stroke to the extent that Merck had to give up on its development.
“MIV-711 is a potent and selective inhibitor of cathepsin K, the principal protease involved in breaking down collagen in bone and cartilage. It is being developed to slow or reverse the progressive degeneration of joints affected by osteoarthritis, and is therefore referred to as a Disease Modifying Osteoarthritis Drug (DMOAD). Since there are no DMOADs approved for use currently, the standard of care for osteoarthritis patients is based on changes in lifestyle and the use of analgesics. The long-term use of analgesics by osteoarthritis patients is associated with an increased risk of side effects such as gastrointestinal bleeding and opioid dependency. DMOADs therefore represent a very large and attractive market opportunity. Medivir estimates that the US market alone is greater than USD 6 billion annually for a drug that impacts disease progression, even if its use was restricted to patient populations with moderate osteoarthritis in weight-bearing joints.
About the MIV-711 phase IIa studies
MIV-711-201 was a randomized, double-blind, placebo-controlled phase IIa clinical trial evaluating the safety and efficacy of 6 months of treatment with MIV-711 compared to placebo for the treatment of patients with moderate knee osteoarthritis. MIV-711-201 enrolled 244 patients. The primary endpoint was the change in patient-reported average knee pain.”2
Participants were divided between a control group and two groups taking different doses of MIV-711: 100 or 200 mg once daily over the six month period. At the end of the study, those on the drug showed a 65% reduction in bone loss, regardless of dosage. Participants on the highest dose of the drug experienced a slight increase in cartilage thickness, while those on low doses saw a 70% reduction in median loss of femoral cartilage thickness relative to the placebo group.2
The drug had no impact on the joint pain experienced by participants.
Medivir is actively seeking a partner for the development of MIV-711, touting the billions of dollars they expect to earn once the drug is approved for manufacture. We’ll be keeping an eye out for new developments on this, with the expectation that, as was the case with odanacatib, MIV-711 will also cause terrible side effects.
Running Just One Minute Every Day Could Save Your Bones
Just one minute of intentional and vigorous exercise per day can help women improve their bone health.3 The good news comes from a study conducted at the University of Exeter in England.
Researchers used data from the UK Biobank, a large-scale study that tracks the health information of a pool of participants. For this study, they compared physical activity levels to bone health in 2,500 women using wrist-worn monitors and ultrasound scans.
“The researchers found that those who completed 60 to 120 seconds a day of high-intensity, weight-bearing activity — i.e., a medium-paced run for pre-menopausal females, or a slow jog for post-menopausal women — reaped the rewards of at least 4% better bone health than those who didn’t do such exercise.
“We don’t yet know whether it’s better to accumulate this small amount of exercise in bits throughout each day or all at once, and also whether a slightly longer bout of exercise on one or two days per week is just as good as 1-2 minutes a day,” says lead author Dr. Victoria Stiles, “but there’s a clear link between this kind of high-intensity, weight-bearing exercise and better bone health in women.”4
The study analyzed the women’s physical activity second-by-second to establish the difference between endurance activities and short bursts of exercise. It also found that women who did more than two minutes of high-intensity weight-bearing exercise a day showed six percent better bone health than those who did less than a minute.
It’s no surprise to Savers that weight-bearing exercise creates stronger more resilient bones, but it’s always exciting to have the latest scientific research confirm it.
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Till next time,
1 International Osteoporosis Foundation. “Bone loss after denosumab, only partial protection with zoledronate: Case series of six women with postmenopausal osteoporosis who had received continuous denosumab for seven years and were then given a single infusion of zoledronate..” ScienceDaily. ScienceDaily, 2 August 2017.
2 “Medivir Announces Positive Topline Results from Phase IIa Osteoarthritis Study, Showing Disease-modifying Benefit of MIV-711 on Joint Structure” Press Release. September 25, 2017. Web: https://www.prnewswire.com/news-releases/medivir-announces-positive-topline-results-from-phase-iia-osteoarthritis-study-showing-disease-modifying-benefit-of-miv-711-on-joint-structure-300525422.html
3 Stiles VH, et al. “A small amount of precisely measured high-intensity habitual physical activity predicts bone health in pre- and post-menopausal women in UK Biobank.” International Journal of Epidemiology. June 29, 2017. Web: https://doi.org/10.1093/ije/dyx080
4 Daniel Steingold. “Just One Minute Of High-Intensity Exercise A Day Improves Women’s Bone Health, Study Finds.”. July 31, 2017. Web: https://www.studyfinds.org/minute-exercise-bon