Biotechnology

Five recent advances in osteoporosis research

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Osteoporosis is a condition that causes bones to become very weak, making them more likely to break. In fact, in very serious cases of osteoporosis, even a small cough or bump can cause a fracture. Often referred to as the ‘silent disease’, many people who have this condition won’t realize it until they actually break a bone, usually in the hip, spine, or wrist.

Because bones are made of living tissue, a healthy human body usually breaks down old bone and replaces it with new bone. But in people with osteoporosis, more bone is broken down than replaced.

The inside of our bones is arranged like a honeycomb, and it is this structure that gives bones their strength. When osteoporosis sets in, the ‘honeycomb’ begins to break down, creating unsupported patches inside the bone, meaning only the outer layers hold the bones together.

About 10 million Americans suffer from osteoporosis, and another 44 million have low bone density, putting them at increased risk. The risk of developing osteoporosis also increases with age, with an estimated half of all adults aged 50 and over at risk of fracture.

In addition, women are more at risk of developing osteoporosis than men because hormonal changes during menopause can directly affect bone density, meaning women can rapidly lose bone mass over several years. But in men, the loss of bone mass is generally slower.

Current treatments for osteoporosis include drugs such as bisphosphonates, which work by slowing bone loss. It has been used for two decades to treat and prevent osteoporosis.

Even though treatment options are available, there is still research around osteoporosis that has the potential to lead to new and more effective treatments. Here, we look at some of those studies, exploring five of the most recent advances in osteoporosis research.

Discoveries could lead to new oral treatments for osteoporosis

In a first step toward potentially cheaper, more effective, and easier to implement osteoporosis treatments, a team of drug development scientists from Florida International University’s Herbert Wertheim College of Medicine (FIU), along with a collaborative team from the National Center for Advancing Translational Sciences (NCATS) – part of the National Institutes of Health (NIH) – has identified a possible new way to counter the effects of osteoporosis.

This new method can help bone-producing cells to make more bone, and can 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 reveals that it also plays a role in bone development.

To activate these receptors, the NCATS team had to determine the correct chemical compound, so they used robots to screen small molecules from more than 80,000 different compounds, before chemists then tested hundreds of variations until they found the right match.

The researchers then tested it on a mouse model in the lab, which showed a marked increase in bone density.

Research finds delivery of estrogen to broken bones can speed up healing in postmenopausal rats

As previously mentioned, osteoporosis is more common in women than men due to menopause, and fractures in older women also heal more slowly than men.

In fact, three-quarters of adults aged 65 and over who suffer hip fractures each year in the US are women, and it is estimated between 15% and 36% hip fracture patients die within one year.

But now a research team has found that estrogen can actually help speed up the healing process of broken bones; they found that a single local delivery of estrogen to fractures accelerated healing in menopausal mice, which could change the way women are treated for fractures in the future.

Here, the researchers wanted to answer the question of why women heal differently than men, leading them to investigate stem cells as a potential culprit in the different healing outcomes, due to the fact that men’s and women’s immune systems differ slightly and that of a person. originate from their bone marrow.

From this, they found that mouse and human skeletal stem cells are both dependent on estrogen and that estrogen directly regulates bone proliferation at the stem cell level.

In a female mouse model, the team removed the ovaries to induce a menopause-like state, before administering local estrogen to the fracture site using a powdered pill applied directly to the wound.

With this, the researchers were able to restore skeletal stem cells to their initial levels and enhance healing in their ovary-less mouse model.

Scientists pinpoint a key driver of low bone density that could lead to better care for women with osteoporosis

In even more recent osteoporosis research, scientists from the Van Andel Institute have been able to find a major cause of low bone density that could lead to better treatments with fewer side effects for women with osteoporosis.

The study here revealed that loss of KDM5C – an epigenetic modulator – preserves bone mass in mice. KDM5C works by switching epigenetic ‘signals’, similar to ‘on’ and ‘off’ switches, which ensure instructions written in DNA are used at the right time, and in the right place.

For the study, the researchers looked at why women experience disproportionately lower bone mass than men throughout their lives, observing differences in the way bones are arranged in male and female mice.

They found that reducing KDM5C interfered with cellular energy production in osteoclasts — the cells that basically help your bones grow, develop, and regenerate. This, in turn, slows down the recycling process and preserves bone mass.

In addition, KDM5C is significantly linked to the X chromosome, which means it is more active in women than men.

Rani Therapeutics announced positive results from part 2 of its phase 1 trial for an osteoporosis drug

Parathyroid hormone (PTH) has been shown to be an effective anabolic treatment for osteoporosis, but, currently, patients who are prescribed PTH must be injected daily, which is much more onerous than taking capsules.

Rani Therapeutics is a clinical stage biotherapy company, and is developing RT-102, namely RaniPill GO capsules under development for the treatment of osteoporosis, which contain a proprietary formulation of a human parathyroid hormone analogue (1-34).

Late last year, the company announced positive topline results from part 2 of its phase 1 RT-102 study, with the study having reached 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 load 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 postmenopausal – who completed seven days of consecutive dosing, the capsules demonstrated an overall drug delivery success rate of 91% over seven days, and, on day seven – with sampling more frequent serial drugs after swallowing the capsules on the day – the success rate of drug administration is 100%.

The company now expects to start phase 2 trials at some point this year.

The new model can predict the best combination of osteoporosis drugs

There are currently several types of medications available to treat postmenopausal bone loss, which can be combined if needed. However, there is little evidence to suggest that combination treatment is best for patients with postmenopausal osteoporosis.

But now, scientists have developed a new mathematical model that could help doctors decide the best drug combinations and the order in which they should be used, potentially improving outcomes for patients and reducing the risk of side effects. It can also allow for more personalized treatment regimens to be created depending on the individual.

To achieve this, the researchers created a mathematical model of bone renewal that predicts the effects of various osteoporosis medications in postmenopausal women. This model is based on recent evidence about how old bone is broken down and new bone made, and how different types of osteoporosis drugs work.

They then tested the effects of rearranging different drug sequences, with the model showing that some combinations given in certain sequences worked better than others.

Plus, they found that the combination that caused the most rapid increase in bone density did not always strengthen the bones in the long term, instead potentially causing a rebound of accelerated bone loss after treatment ended.

New technologies related to osteoporosis research (supported by IN-PART)

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