May 10 2007 post. It always helps to reread studies. Yesterday I had a second look at a study on curcumin and bone resorption published in 2004 in the Journal of Immunology (http://tinyurl.com/ynuvw7), according to which curcumin may be helpful in treating secondary bone lesions associated with breast cancer and multiple myeloma and those associated with nonmalignant diseases like postmenopausal osteoporosis, Paget’s disease and rheumatoid arthritis Researchers examined the effects of curcumin on RANKL, which stands for: Receptor Activator for Nuclear Factor-kB Ligand. Before proceeding, though, what does RANKL have to do with MM? MM cells can stimulate this receptor activator: the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease. (See: http://tinyurl.com/36evhl) Therefore, news of any RANKL inhibitor is GOOD news. And it just so happens that, according to the abovementioned Journal of Immunology study, RANKL induces osteoclastogenesis through the activation of NF-kB, and treatment with curcumin inhibits both the NF-kB activation and osteoclastogenesis induced by RANKL. Perfect.
I also read about a 2006 University of Arizona study (head researcher: Dr. Janet Funk) on bone loss and curcumin, see http://tinyurl.com/28cpqj. Bone loss is a big problem in MM. The proliferation of MM cells reaches the point of inhibiting the regular functioning of bone-forming cells. As a result we may develop lytic lesions, which look like holes (!) and put us at a great risk for fractures, not to mention pain. Under normal circumstances, osteoclasts (about which I have written in my post on ginger) are cells that rebuild what is called fatigued bone, with the help of osteoblasts. In MM, osteoclast activity is increased (bad bad bad!), which causes bone loss instead of bone repair. (I don’t want to get bogged down in the details of this process, which is well explained here: http://tinyurl.com/2894en) I found another study with the same results, i.e., curcumin induces apoptosis of osteoclasts: http://tinyurl.com/2r38aa What is relevant for us MMers, and indeed for anybody suffering from osteoporosis, is that curcumin inhibits excessive osteoclast formation. Excellent! A few more feathers in curcumin’s rather large cap, I’d say.
Now, in all fairness, I also read a study (http://tinyurl.com/2jwu63) that seems to indicate that curcumin inhibits the proliferation and mineralization of osteoblasts. If proved true, this would mean that curcumin might have opposing effects, which, however, might end up annulling each other (I may really be going out on a limb, here! ). That is, no bone loss but no gain, either. Among other things, the following study indicates that arthritic rats treated with curcumin showed improved mineral bone density: http://tinyurl.com/2tlt38 It will be interesting to see future developments based on studies carried out on actual human beings instead of rats and cell cultures. Of course, since I have been taking 8 grams of curcumin for more than 16 months and my most recent skeletal survey showed no lesions, I have the feeling that Dr. Funk’s research will turn out to be the winner. The eternal optimist!
June 15 2008 post. On Sherlock’s wise recommendation, my most recent set of tests (April) included a set of osteoporosis ones. I have two good reasons to be on top of my bone health: 1. my mother, who is almost 80 years old, has osteoporosis, and 2. as we know, myeloma weakens and damages the bones, causing bone pain, fractures and hypercalcemia (too much calcium in the blood due to bone destruction). Bone pain, in fact, is the most common symptom of myeloma at the time of diagnosis.
Well, those results were all within normal limits except for one: my parathyroid hormone levels, paratormone in Italian, were a bit on the high side. Para-whaaat? I had to look this up online. Never heard of it before.
The parathyroid glands are four tiny glands located in the neck. As I learned from an excellent website (http://tinyurl.com/68×78n), they have nothing to do with the thyroid gland except for location: Parathyroid glands are small glands of the endocrine system which are located in the neck behind the thyroid. The thyroid gland controls body metabolism whereas the parathyroid glands control body calcium and phosphorus levels. These four glands produce the parathyroid hormone (PTH) whose only function is to control calcium levels in the blood. If our body calcium is low, the glands produce more PTH to raise calcium levels. If blood calcium levels rise, though, the glands decrease PTH production. This is the normal situation.
But sometimes one or more of the glands can develop a benign tumour that causes it/them to secrete more PTH than needed. Blood calcium consequently rises. This is called primary hyperparathyroidism. The risk of osteoporosis and fractures increases. This is not my case: my blood calcium is the lowest it has ever been.
Secondary hyperparathyroidism or SHPT is instead caused by long-term low levels of blood calcium. It is typical of people with chronic renal failure (again, not my case) or with vitamin D deficiency. Aha! That could well be my case, since SHPT blood tests show elevated parathyroid hormone levels but low or normal calcium levels.
Of course, I also checked Internet to see if there was a connection between hyperparathyroidism and myeloma. There is. This makes sense when you consider that one of the symptoms of myeloma is too much calcium in the blood, as we have seen. But usually, when myeloma patients’ parathyroid levels are high, so are their calcium levels. Not my case. So I was able to exclude myeloma as a cause for my overly active parathyroid glands.
Since I am not a medical doctor, though, at times my interpretation of test results requires confirmation. To make a long story short, I went to see an endocrinologist yesterday morning. I had never been to an endocrinologist. It turned out to be a very interesting visit.
She didn’t seem overly concerned about my highish parathyroid hormone result but told me that it could be caused by one of two things: a. lack of vitamin D (bingo!), or b. a batty gland that can be removed…surgically. Obviously, I hope option “a” turns out to be the correct one. So, what do I need to do? Easy peasy: stop taking vitamin D for 3-4 months and then have my tests repeated. If my parathyroid level increases, that would confirm a diagnosis of vitamin D deficiency. If not, then we will consider the whacky gland option.
The endocrinologist told me that, if she were in my situation, she would do exactly what I am doing–take curcumin etc. (how about that?!!!). She was very matter-of-fact and used very simple words to describe active myeloma as a form of (very very very bad!) osteoporosis that erodes the bone from within. While destroying the bone, it also prevents bone reformation. Nothing new to me, but I was impressed by her knowledge of this cancer.
She also told me that specialists, from haematologists to radiologists, tend to shut themselves inside their highly focused specialistic box and forget to peek outside that little box. She instead strongly believes that it is dangerous to forget that patients may have other things going on that affect their general state of health and that could also be affecting the specific condition under treatment—myeloma or whatnot. She said that we must take care of health issues before they turn into problems instead of waiting until it’s too late. Of course, that is not always possible, but in my case it is because I was diagnosed early.
She told me that we should be “well-equipped” in case my myeloma becomes active some day. I certainly didn’t argue with that!
In conclusion, I would like to recommend…indeed, highly recommend!…that every myeloma patient go to an endocrinologist and have bone-related tests. Take care of your bones to prevent possible future problems. Of course, those of us who are lucky to be asymptomatic hope to remain so and never develop any of the problems related to this cancer. But…just in case…!!!
September 8 2008 post: Last week Sherlock sent me a German study that confirms what I read in other studies that I posted about more than a year ago (on May 10 2007, to be precise). The German study was published in the “Journal of Cancer Research and Clinical Oncology” last month (see abstract: http://tinyurl.com/6xnp7y). It opens with the hypothesis that curcumin lessens osteoclast differentiation and function. If true, that would be a good good good (!) thing.
Well, I am happy to report that this hypothesis was indeed confirmed by test results, which showed that Curcumin inhibits RANKL-induced osteoclast differentiation and resorptional activity in a dose-dependent manner. Then, in the “Discussion” part, we read that Bone is a dynamic organ which is continuously remodelled by resorption of primary bone and build-up of new bone, a process that requires coordinated cross-talk between osteoclasts and osteoblasts. Okay, I will attempt to put this into simpler (?) words.
Osteoclasts are a type of bone cell that break down bone in a process known as bone resorption, while their counterpart, called osteoblasts, rebuild it. This is a perfectly normal state of affairs in healthy folks. In abnormal cases such as cancer and inflammatory diseases, though, an unbalance occurs: osteoclast activity increases…and the number of osteoblasts decreases. In other words, there are not enough osteoblasts to rebuild the bone that is being destroyed by the pesky little osteoclasts. One of the consequences is that bone calcium gets “chipped off” and released into the bloodstream. We know what that means!
Ah, a quick reminder about RANKL, too. The acronym stands for “Receptor Activator for Nuclear Factor-kappaB Ligand.” It’s a protein that activates osteoclasts and is thus important in bone metabolism. Under normal circumstances, this is not a problem. But in the case of myeloma, for instance, a vicious cycle forms. Myeloma cells overstimulate RANKL, which in turn overstimulates the formation of osteoclasts, and we know what happens at that point: bone lesions. RANKL is thus a therapeutic target, and that is why, in my opinion, the recent confirmation that curcumin inhibits this mischievous protein is an excellent bit of news!
The German researchers also treated osteoclasts with curcumin, stimulated them with RANKL and observed a reduction of NF-kB binding activity. Even if we don’t understand this bit, or understand it only in part, the point is that this is all very good news, which can be summarized as follows:
curcumin hinders the process of bone destruction.