High Sclerostin Levels Linked To Advanced Disease And Poor Bone Formation In Multiple Myeloma Patients
Results of a recent Greek study show that high levels of the protein sclerostin in the blood are associated with advanced disease and poor bone formation in multiple myeloma patients.
In addition, the results indicate that Velcade may be effective in reducing sclerostin levels in myeloma patients.
“Our study has shown that sclerostin is increased in myeloma patients, and together with the [laboratory] data presented at the last ASH meeting, suggests that sclerostin inhibits the function of [bone-building cells] in myeloma,” said Dr. Evangelos Terpos of the Alexandra General Hospital in Athens, Greece, and lead author of the study.
“Based on [our results], antibodies against sclerostin may be given in Phase 1 studies in the treatment of multiple myeloma. That is, I think, the major contribution of [our study],” he added.
Dr. Ken Shain of the Moffitt Cancer Center in Tampa, Florida, who was not involved in the study, agreed that the results would help to identify antibodies and other potential agents for the treatment of bone disease in multiple myeloma.
“[This study may help to] increase the number of agents we can use against bone disease in myeloma,” said Dr. Shain.
“If [targeting sclerostin] leads to improvements in current bone disease or prevents bone disease from occurring, we are going to be better off. The more therapeutic options we have, the better off myeloma patients will be in the long run,” he added.
Nearly 80 percent of myeloma patients have evidence of bone loss when they are first diagnosed with myeloma, and bone disease is one of the most challenging complications of myeloma.
In multiple myeloma, bone disease occurs because of an imbalance between bone-building cells (osteoblasts) and bone-destroying cells (osteoclasts).
Specifically, bone-destroying cells are favored over bone-building cells in myeloma patients because proteins called “Wnt inhibitors” interfere with the pathways involved in the functioning of bone-building cells.
One such Wnt inhibitor, DKK-1, is considered a promising target for new myeloma bone disease treatments (see related Beacon news).
Sclerostin is another Wnt inhibitor that is produced by mature bone cells and inhibits bone formation. In recent years, elevated sclerostin levels have been found in patients with osteoporosis and other bone diseases not related to myeloma.
There is not much concrete information, however, about the role of sclerostin in multiple myeloma.
According to Dr. Shain, it is important to determine whether myeloma cells directly cause the increased production of sclerostin in myeloma patients.
“[We need to determine] if sclerostin is truly a [cause] of bone disease in multiple myeloma or just a marker of bone disease. If sclerostin is not actively causing bone disease, then it is not an appropriate target [for therapy],” commented Dr. Shain.
Results of recent laboratory studies have suggested that myeloma cells may be directly involved in the production of sclerostin.
One study showed an increase in sclerostin production when bone marrow cells were placed in the same environment as human myeloma cells. This suggests that the interaction between myeloma cells and bone marrow cells results in elevated sclerostin levels, contributing to bone disease in myeloma patients.
Another study revealed that myeloma cells cause sclerostin-producing bone cells to die, and that sclerostin is released into the blood when these bone cells are destroyed.
In the current study, Greek researchers investigated the role of sclerostin in myeloma patients and explored whether clinical observations would be in line with the recent laboratory data.
The study included 224 participants: 157 newly diagnosed multiple myeloma patients, 25 relapsed multiple myeloma patients, 21 patients with monoclonal gammopathy of undetermined significance (MGUS), and 21 healthy individuals. The median age of the study participants was 68 years.
The newly diagnosed myeloma patients received a median of three lines of therapy during the course of the study. Eighty-seven percent of these patients received conventional chemotherapy as first-line therapy, and the remaining 13 percent of patients received treatment with different combinations of novel agents. In addition, 21 percent of patients received a stem cell transplant.
The relapsed myeloma patients had previously received between one and three lines of therapy. All relapsed myeloma patients received four cycles of Velcade (bortezomib) monotherapy during the course of the study.
Blood samples were collected from the newly diagnosed myeloma patients and the MGUS patients one week from diagnosis. Blood samples were also collected from the relapsed myeloma patients, once on the first day of treatment with Velcade and once near the end of treatment.
The study authors found that the newly diagnosed myeloma patients had higher levels of sclerostin than the MGUS patients and the healthy participants in the trial.
Moreover, patients who had either advanced bone disease or fractures at diagnosis had higher sclerostin levels compared to all other patients.
In addition, patients with more advanced stages of multiple myeloma also had higher sclerostin levels than patients with less advanced stages of myeloma.
The median overall survival time for newly diagnosed patients was 48 months. Patients with high sclerostin levels had significantly shorter overall survival times than patients with lower sclerostin levels (27 months versus 98 months).
Forty-four percent of the relapsed myeloma patients responded to Velcade monotherapy, including 8 percent who achieved a total response.
Sclerostin levels decreased in patients who responded to Velcade as well as those who did not respond to Velcade (47 percent and 51 percent, respectively). According to the study authors, this may be a sign that Velcade can reverse bone formation abnormalities in myeloma.
For more information, please see the full article in the International Journal of Cancer (abstract).
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My sister was diagnosed with Multiple Myeloma in June 2009. It was a disease our family had not heard of and her diagnosis was incidental, her rheumatologist had noticed elevated protein levels in her blood and suggested it should be checked. When diagnosed the oncologist told her she had 3 to 5 year to live and at 57 her whole world tumbled around her. She is such a determined lady and the Myeloma journey she is facing has been endured without any complaint. The doctors adopted a watch and wait policy, but now in the last week has commenced treatment with Dexamethasone and thalidomide. As a family we are constantly on the watch for any changes but her remarkable attitude is a source of inspiration. The comments of your readers is also inspiring, they show there is light at the end of the tunnel and that there is an opportunity to return to some nomality in your life. I do agree with Pat, wisdom is a wonderful weapon and with knowledge acquired from Forums such as this and speaking with other patients, we are working to prove the doctor's original diagnosis wrong.
Dear Readers,
I am a 60 year old African American felmale.I am obese, 210 lbs and 5'2" although I am told by close friends that I seem shorter than I use to be.
I have excruciating bone pain. My bones ache in my arms; upper and lower, thighs and legs, even mhy feet. I do have some joint pain as well. I have minor swelling. Also I have pain in my ribs, especially when touched. When I am lying down on my side my hips hurt.I have some type of degenerative backbone problem. I had liver surgery for a tumor that had enveloped my liver about three years ago.
I also seem to have cysts in my right arm. Although there are several lumps in my arm, two of them are painful and are deeper than the other ones. I have pain in my right side but the pain is very deep .
I suspect that I have Multiple Myeloma or MBD. I have had horrible bone pain. I have been told that I am hyperuricemic and have very low Vitamin D levels.My calcium levels seem to fluctuate from within normal to 10.9.
I also have a high sedimentation rate, and metabolic rates are reported as abnormal Being overweight, I am reluctant to take steroids. I am also afraid of celebrex, since there have been quite a few negative reports.
I have a prescription to lower my uric acid level and raise my vitamin D level, but noone is looking into why I have these problems in the first place.
Test completed are are blood tests, MRI, which said I had slight bone degeration on my left shoulder blade and something with my foot but otherwise norma. . XRay and bone scan for osteoporosis were also given and results were negative. . I have not had an urine analysis, although the last few that I took said that there was blood in my urine, even though not visible to the naked eye, that was about a year and half ago. I went to a bone specialist but he sent me to a Rhematologist.
Thank you for your ihformation. Although I feel like I am in some kind of pre-diagnose limbo, I am glad that I can get information from such a valuable organization such as yours. Thank you.
Fearful and frustrated,
Brenda
Hi Brenda....I hope you don't have cancer of any sort, but if you do, this is a good website to help with understanding MM. hope you get some sort of definition about your health soon, and then can get into the appropriate treatments. Best of luck!
Dear Brenda,
Thank you very much for your kind words regarding The Beacon.
We are very sorry to hear that you are fearful and frustrated. We understand that not knowing what you are dealing with is the most difficult stage of disease.
We encourage you to visit our forums and share your experiences and questions there:
http://www.myelomabeacon.com/forum/
Our readers and the Beacon's Medical Advisors, who are myeloma specialists, have a great deal of knowledge and experience that you may find very useful.
Please let us know if there is anything else we can do for you. Best wishes.
Brenda,
I am sorry to hear your frustration and know what you are going through. I was followed by a rheumatologist for many years of unusual symptoms, low vit D & high sed rate. It was originally thought I had an autoimmune disease but all tests did not confirm, so was followed as an undetermined autoimmune for many years. Two years ago a serum protein was done with slight abnormality but was just followed. This year after it was done again, I was referred to hematologist which followed up with tests with MM diagnosis and confirmed in May, 2009 with Bone Marrow Biopsy. I am a bit unusual because I had not met any of the CRAB criteria but had 70% cells in BMB. I received a second opinion in July at Dana Farber and the recommendation with the high BMB is to start treatment right away, but I held off a couple of months and observed labs. It became obvious in November that it was shifting so I have started treated at Duke's Done Marrow Transplant Center in December with Rev/Velcade/Dex. I have just started cycle 2 and happy with lab results from cycle 1.
I think you should see if you can be referred to hematologist who could do approprite lab results to confirm or rule out this. As disappointed as I was with my diagnosis, I was not surprised because I had been frustrated for so many years knowing it was something and it could not be diagnosed. I wish you the best of luck in your journey!
Hello,sorry to hear your pain.My brother was just diagonsed this morning,our family never heard of any thing like this before.He is in so much pain.They are sitting him up for surgery as I type im really nervous about this also.They also say that he has a liver disease.But I pray for you and your family as well as my brother he is so young.But know days it doesn't matter your age.
praying for you
Linda