Osteoporosis is a condition that causes bones to become extremely weak, making them more likely to break. In fact, in extremely serious cases of osteoporosis, even a cough or a minor bump can result in a fracture. Often referred to as a ‘silent disease’, many people who develop the condition will not be aware they have it until a bone actually breaks, usually in the hip, spine or wrist.
Because bones are made of living tissue, a healthy human body will usually break down old bone and replace it with new bone. But in people with osteoporosis, more bone is broken down than is replaced.
The inside of our bones is structured like a honeycomb, and this structure is what gives bones their strength. When osteoporosis occurs, the ‘honeycomb’ starts to break down, creating patches within the bone that are unsupported, meaning the outer layer is all that is holding the bone together.
Approximately 10 million Americans have osteoporosis, and another 44 million have low bone density, putting them at an increased risk. The risk of developing osteoporosis also increases as people get older, with an estimated half of all adults aged 50 and over at risk of breaking a bone.
Additionally, women are more at risk of developing osteoporosis than men because hormone changes during menopause can directly affect bone density, meaning women may quickly lose bone mass for several years. In men, however, the loss of bone mass is generally slower.
Current treatments for osteoporosis include medications such as bisphosphonates, which work by slowing bone loss. These have been used for two decades to treat and prevent osteoporosis.
Despite treatment options already available, there is still ongoing research around osteoporosis that could potentially lead to new and more effective treatments. Here, we take a look at some of that research, exploring five of the latest advancements in osteoporosis research.
Table of contents
Discovery could lead to new oral treatment for osteoporosis
In the first step towards potentially cheaper, more effective and easier-to-take treatments for osteoporosis, a team of drug development scientists from Florida International University’s (FIU) Herbert Wertheim College of Medicine, along with a collaborative research team from the National Center for Advancing Translational Sciences (NCATS) – part of the National Institutes of Health (NIH) – have identified a possible new way to counteract the effects of osteoporosis.
The new method can help bone-producing cells to make more bone, and could be taken orally, as a pill.
To allow bone-producing cells to make more bone, the researchers targeted a hormone receptor called relaxin family peptide receptor 2 (RXFP2), which is known to play a role in the formation of reproductive organs. And, further research revealed that it also plays a role in bone development too.
In order to activate this receptor, the NCATS team had to pinpoint the right chemical compound, so they used robots to screen for small molecules from more than 80,000 different compounds, before chemists then tested hundreds of variations until they found the correct match.
Researchers then tested it on mouse models in the lab, which demonstrated a marked improvement in bone density.
Research finds delivery of estrogen to a fracture can speed up healing in postmenopausal mice
As mentioned previously, osteoporosis is more common in women than men due to the menopause, and bone fractures in older women also heal more slowly than in men.
In fact, three-quarters of adults aged 65 or older who suffer hip fractures each year in the U.S. are women, and it is thought that between 15% and 36% of hip fracture patients die within a year.
But now a team of researchers have found that estrogen could actually help speed up the bone fracture healing process; they discovered that a single, localized delivery of estrogen to a fracture sped up healing in menopausal mice, which could change the way women are treated for fractures in the future.
Here, researchers wanted to address the question of why women may heal differently from men, leading them to investigate stem cells as a potential culprit in the different healing outcomes, due to the fact that men and women’s immune systems differ slightly and a person’s immune system is derived from their bone marrow.
From this, they found that both mouse and human skeletal stem cells are estrogen dependent and that estrogen directly regulates bone proliferation at the stem cell level.
In the female mouse models, the team removed the ovaries to induce a menopausal-like state, before giving localized estrogen to a fracture site using a pulverized pill applied directly to the wound.
With this, the researchers were able to restore skeletal stem cells to baseline levels and increase healing in the mouse models without their ovaries.
New research pinpoints key driver of low bone density that could lead to improved treatments for women with osteoporosis
In yet more recent osteoporosis research, scientists from the Van Andel Institute have managed to pinpoint a key driver of low bone density that could lead to improved treatments with fewer side effects for women with osteoporosis.
The research here reveals that the loss of KDM5C – an epigenetic modulator – preserves bone mass in mice. KDM5C works by altering epigenetic ‘marks’, akin to ‘on’ and ‘off’ switches, that ensure the instructions written in DNA are used at the right time, as well as in the right place.
For the study, the researchers looked at why women experience disproportionately lower bone mass than men throughout their lives, observing the differences in the ways bone is regulated in male and female mice.
They found that reducing KDM5C disrupted cellular energy production in osteoclasts – cells that essentially help your bones grow, develop and regenerate. This, in turn, slowed down the recycling process and preserved bone mass.
Additionally, KDM5C is significantly linked to X chromosomes, meaning it is more active in women than in men.
Rani Therapeutics announces positive results from part 2 of a phase 1 trial for osteoporosis drug
The parathyroid hormone (PTH) has been shown to be an effective anabolic treatment for osteoporosis, but, currently, patients who are prescribed PTH must have injections administered daily, which is much more of a burden than taking a capsule.
Rani Therapeutics is a clinical-stage biotherapeutics company, and is developing RT-102, which is the RaniPill GO capsule being developed for the treatment of osteoporosis, containing a proprietary formulation of human parathyroid hormone (1-34) analog.
Late last year, the company announced positive topline results from part 2 of its phase 1 study of RT-102, with the study having achieved all of its endpoints.
It was found that the drug was generally well-tolerated with no serious adverse events noted during the study, plus the drug payload was delivered with high reliability and with bioavailability comparable to, or better than, subcutaneous injection.
In all 10 participants – who were healthy female volunteers, with five also being postmenopausal – who completed seven days of daily, consecutive dosing, the capsule demonstrated an overall drug delivery success rate of 91% over the seven days, and, on day seven – with more frequent, serial drug sampling after capsule swallowing on that day – the drug delivery success rate was 100%.
The company is now expecting to initiate a phase 2 trial at some point this year.
New model can predict best osteoporosis drug combinations
There are currently several types of drugs available to treat postmenopausal bone loss, which can be combined if necessary. However, there has been little evidence to suggest what the best treatment combinations might actually be for patients with postmenopausal osteoporosis.
Now though, scientists have developed a new mathematical model that may help clinicians decide on the best combination of medications and the order they should be taken in, which can potentially improve outcomes for patients and reduce the risk of side effects. It could also allow for more personalized treatment regimens to be created depending on the individual.
To achieve this, the researchers built a mathematical model of bone renewal that predicts the effects of a variety of osteoporosis medications in postmenopausal women. The model was based on the latest evidence of how old bone breaks down and new bone is created, and how different types of osteoporosis medications work.
They then tested the effects of re-arranging the order of different medications, with the model showing that some combinations given in a particular order worked better than others.
Plus, they discovered that combinations that cause the most rapid increases in bone density do not necessarily always strengthen the bone in the long term, instead can potentially cause a rebound of accelerated bone loss once treatment ends.
New technologies related to osteoporosis research
- Aptamers for the Treatment of Osteoporosis – The University of Hong Kong
- Nanobody Conjugate Therapeutic for Osteoporosis – Boston Children’s Hospital
- Dual Inhibition of Plexin-B1 and Plexin-B2 – Max Planck Society
- Application of PTH (1-34) as a New Drug for Osteoarthritis Treatment – National Sun Yat-sen University