Antibody could reduce bone fractures in MM

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.”