Paget’s Disease of Bone
Paget’s disease of bone is a chronic condition in one or more bones. Usually there are one or two bones that are affected, almost never the entire skeleton.
The disease interferes with your body’s normal recycling process, in which new bone tissue gradually replaces old bone tissue. Bone is a dynamic and active tissue and small-scale changes in bone occur continuously. Normally, as people grow older, their bones rebuild at a slower rate. If you have Paget’s disease, however, this process of rebuilding the involved bones takes place at an accelerated rate. As a result, the rebuilt bone has an abnormal structure. The involved bone can be soft, leading to weakness and bending of the bone. Or, the rebuilt bone can enlarge, making it more susceptible to arthritis, hearing loss, fractures and discomfort. So over time, the disease can cause affected bones to become fragile and misshapen.
Paget’s disease of bone most commonly occurs in the pelvis, low back (spine), hips, thighs, skull, legs and arms.
The complaints with Paget’s bone disease differ from person to person. People sometimes have no specific complaints and the diagnosis is made by chance by the doctor. Signs of Paget’s disease of bone include: pain in bones and joints, headaches, hearing loss, enlargement or bowing of bones, tingling or numbness.
Complications of Paget’s disease of bone can include broken bones, hearing loss and pinched nerves in your spine.
The risk of Paget’s disease of bone increases with age. Given that the disease mostly occurs in people over the age of 40, the symptoms often are mistaken for changes associated with aging. Your risk also increases if any family members have the disorder.
- Use of drugs and adherence
- Alternative treatments
- Living with your illness
- Video I Amgen I Introduction to Bone Biology
- Video I Amgen I Osteoblasts and Osteoclasts
- Video I Amgen I Bone Remodeling and Modeling
- Video I Amgen I Regulation of Osteoclast Activity
- Video I Amgen I Sclerostin
- Video I Amgen I Anatomy of a Fracture as a Result of Systemic Bone Loss
- Video I Intelecom Learning I Development of Bone
- Videos sources
Cause of Paget’s disease of bone
Bone is a dynamic and active tissue and small-scale changes in bone occur continuously. Bones have different functions and they give support to our body. They protect our organs. They make sure we can move. They are a repository for minerals and they are important for the formation of blood cells. Red blood cells, most white blood cells and platelets form in the bone marrow, the soft fatty tissue in the bone cavity. Bone is thus a dynamic and active tissue and small-scale changes in bone occur continuously.
Bone is living tissue with three types of cells.
• Osteoblasts are located on the surface of the bone and ensure the construction of bone tissue. The osteoblasts produce the intermediate. When an osteoblast is completely surrounded by intermediates, we speak of an osteocyte.
• Osteocytes are bone cells that are surrounded by intermediates. These bone cells lie in cavities in the intermediate material. The cells are interconnected via a network of small channels. This network ensures the supply of nutrients and the removal of waste in the bone.
• Osteoclasts are responsible for the breakdown of bone tissue. These are large cells with many cell nuclei. The cells release acids and enzymes that dissolve the interstitial tissue of the bone tissue.
Paget’s disease of bone
Paget’s disease of bone interferes with the body’s normal recycling process in which new bone tissue gradually replaces old bone tissue. Normally, as people get older, their bones rebuild at a slower rate. But Paget’s disease interferes with your body’s normal recycling process.
If you have this disease, this process of rebuilding the involved bones takes place at an accelerated rate. An accelerated effect occurs when cells that normally break down the bone (osteoclasts) become overcrowded at the same time in the same place. The osteoclasts start breaking down the bone tissue with increased speed. The bone production cells (osteoblasts) cannot keep up with this accelerated pace, creating a chaotic bone that is less strong. As a result, the rebuilt bone has an abnormal structure. The involved bone can be soft, leading to weakness and bending of the bone. Or, the rebuilt bone can enlarge, making it more susceptible to arthritis, hearing loss, fractures and discomfort. So over time, the disease can cause affected bones to become fragile and misshapen.
This can lead to problems such as pain in bones and joints, headaches, bending bones (enlargement or bowing of bones), breaking bones (fractures), tingling or numbness, pinched nerves in spine, arthritis and reduced hearing (hearing loss). Paget’s disease of bone most commonly occurs in the pelvis, low back (spine), hips, thighs, skull, legs and arms.
Risk of Paget’s disease of bone
The risk of Paget’s disease of bone increases with age. Given that the disease mostly occurs in people over the age of 40, the symptoms often are mistaken for changes associated with aging.
Hereditary factors probably play a role, because your risk also increases if any family members have the disorder. The disease incidence often involves more than one member of a family in 30% of the cases. Also Paget’s disease occurs more commonly in European populations and their descendants.
Scientific research has shown that a virus infection may also play a role in the development of Paget’s disease of bone. The hereditary factor is perhaps involved when activated by exposure to a virus as the disease is rarely discovered in individuals before they reach age 40 and the number of people identified increases in each progressive age group.
Image ID 119389940 © Igor Zakharevich | Dreamstime.com
Complaints in Paget’s disease of bone
The complaints with Paget’s disease of bone can differ from person to person. This disease can lead to problems such as pain in bones and joints, headaches, bending bones (enlargement or bowing of bones), breaking bones (fractures), tingling or numbness, pinched nerves in spine, arthritis and reduced hearing (hearing loss).
Pain in the bone or joint
If there are complaints, pain in the bone or joint is the most important complaint. The pain complaints differ from person to person. The pain is caused by the activity of the disease, by osteoarthritis and by deformations of the bones and near joints.
Distortion of the bone
If your long leg bones are affected, they can distort. This is because your bone is less firm there. Your joint will now be charged differently and osteoarthritis will develop more quickly.
Bone deformation together with poor bone quality can result in bone fractures. The pain is burning, hot and deep. There is no relationship between the amount of affected bone and the degree to which you may have pain. Characteristic is that the pain does not disappear by resting. This way your skin may feel burning and be oversensitive. In the affected bone the blood flow is often increased.
Location of bone disease
Complaints are often dependent on where the disease is located. The disease can manifest itself in every bone, but it is most common in the skull, the spine, the pelvis, arms and the upper and lower legs. If your skull is affected, you may suffer from headaches, ringing in the ears, dizziness, hearing problems and problems with your eyesight. If your dorsal vertebrae or your pelvis are affected, you will mainly suffer from pain and stiffness. If a diseased vertebra changes shape, a nerve can become trapped. This can cause you to suffer from tingling or numbness. In some cases, acute back pain is caused by a vertebral fracture. Sometimes you suffer from muscle pain because the bone to which the muscle is stuck is deformed. The muscles are thus taxed differently.
Occasionally there are rare complications, such as an overload of the heart because the blood circulation in the affected bones is increased. In very rare situations, if there is no treatment for bone disease, bone damage can lead to cancer in less than 1% of people.
Diagnosis in Paget’s disease of bone
Your doctor will base your diagnosis on a combination of the medical history, his findings and additional test results.
At the first visit, the doctor asks you a number of questions to get a good picture of your condition. You can think of the following questions:
– When did your complaints start?
– Can you describe your complaints?
– How are your working conditions?
– What medication do you use?
– Do rheumatic diseases occur in your family?
– What is your medical history?
– Are you under the treatment of other specialists and for what?
Paget’s disease often causes an arthritic condition and can be diagnosed and treated by doctors who focus on bone disorders. It is the appearance of the affected bones on an X-ray that signals the doctor to make the diagnosis.
A disruption in bone production and/or bone destruction is visible in the blood. Substances that are released by bone destruction can be measured in your blood or urine. Blood tests taken most often will indicate an increase in serum alkaline phosphatase (SAP), which is reflective of the rapid new bone turnover. Serum alkaline phosphatase is a protein that is present in an increased amount in bone and liver disorders. An excess amount of serum alkaline phosphatase in your blood is an indication of Paget’s disease of bone and the activity of the disease can also be measured.
Urine test results also will indicate the speed at which the rebuilding of bone is taking place. A disruption in the process of bone building and bone destruction can lead to excessive calcium excretion in your urine.
Doctors usually obtain a non-invasive bone scan to determine the extent of the bone involvement. A radiograph is an image produced on a sensitive plate or film by X-rays, gamma rays, or similar radiation and typically used in medical examination. On the radiograph, the doctor can see which bone is affected, whether there are bone fractures and any wear in adjacent joints is visible. The doctor can determine how active the bone disease is. Sometimes a CT or MRI scan is made to get an accurate picture of bone abnormalities. A small, harmless amount of radioactive material is introduced into your blood. This substance shows the parts of your skeleton that have been affected by the disease.
If Paget’s disease of bone occurs in your immediate family, you can discuss it with your doctor to have your serum alkaline phosphatase measured after age 45.
Paget’s disease of bone is a chronic, benign bone disorder. If there is doubt after the examinations whether the abnormality in the bone is benign and cancer is suspected, it will be necessary to take a bone biopsy of the bone to examine it under a microscope.
Treatment of Paget’s disease of bone
Paget’s disease of bone is slowly progressive and cannot be cured. If the bone disease is not treated and the disease process is not slowed down, you’re function in daily life will worsen due to slow deformation and breaking of bones. Treatment for Paget’s disease can focus on providing physical assistance, including the addition of wedges in the shoe, canes as walking aids, the administration of physical therapy and drug treatment.
Drugs without a prescription
• For the pain you can get a simple painkiller with the active ingredient paracetamol without a prescription. Paracetamol helps against pain and fever, does not cause stomach problems, usually does not cause side effects and can be easily combined with other medications.
• An NSAID, an anti-inflammatory analgesic in a lower dose. The abbreviation NSAID stands for Non-Steroidal Anti-Inflammatory Drugs. These painkillers inhibit inflammation.
Do you have physical complaints? Always go to your doctor or specialist for a proper diagnosis and proper treatment.
Drugs on prescription
This is provided by your doctor or rheumatologist or internist.
Paget’s disease of bone is treated with painkillers and a bisphosphonate. Proper treatment with a bisphosphonate can stop Paget’s bone disease. This reduces the chance that your bone breaks or distorts and new complaints can be prevented. Damage that has already arisen cannot be repaired. A bone that is already deformed cannot be made smaller. It is therefore important to start treatment as early as possible, even if you have no or few complaints. You may still continue to experience symptoms and pain after the treatment because you suffer from permanent deformation of the bone or osteoarthritis that has occurred.
• Acetaminophen. Acetaminophen is a pain reliever and a fever reducer (for example Panadol, Tylenol). Acetaminophen is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers.
• An NSAID, an anti-inflammatory analgesic, such as naproxen or ibuprofen. The abbreviation NSAID stands for Non-Steroidal Anti-Inflammatory Drugs. These are drugs that are effective against inflammation, pain, stiffness and fever, but do not contain corticosteroids (steroids). They do not prevent joint damage. There is no proof that any one NSAID is better than others. Your doctor will prescribe these prescription drugs with a higher dose of the active substance. High doses of short‐acting NSAIDs give the fastest relief of symptoms. Given in the correct dose and duration, these drugs give great relief for most patients. The NSAIDs may cause stomach upset, ulcers or diarrhea, but they are well tolerated by most people when used for the short term. Some people cannot take NSAIDs because of health conditions such as ulcer disease, impaired kidney function or the use of blood thinners.
• Bisphosphonates reduce the pain and help the body regulate the bone-building process to stimulate more normal bone growth. Good treatment with a bisphosphonate can stop the development of Paget’s disease of bone. This reduces the chance that your bone breaks (fracture) or distorts and new complaints can be prevented. Damage that has already arisen, can not be repaired. It is therefore important to start the treatment as early as possible. After treatment, you may still continue to experience symptoms and pain because you suffer from permanent deformation of the bone or osteoarthritis that has occurred.
Bisphosphonates are medications that are also given in osteoporosis and that inhibit bone destruction. The medicine ensures that calcium is absorbed better in the bone. The bone breakdown and the bone production are then more in balance. When bisphosphonates are used, bone density may even increase slightly. Research has shown that the chance of a bone fracture reduces by 50% if you use bisphosphonates. This applies especially to your spine, but also to your hips and other bones, such as your wrist.
There are different types of bisphosphonates, each with its own method of administration. The most commonly used long-acting bisphosphonate in Paget’s disease of bone is zoledronic acid. This brings the bone disease to rest for a long time, sometimes for a few years, and is given once on the day treatment. There may be side effects such as muscle pain, stiffness headache, fever or pain in the affected bone, especially during the first administration. The doctor may also choose to treat you with the bisphosphonate risedronic acid.
Bisphosphonates may have side-effects such as: 1. gastrointestinal complaints such as abdominal pain, heartburn, flatulence, nausea and diarrhea; 2. bowel obstruction; 3. an ulcer in your esophagus, stomach or duodenum. Because any side-effects usually occur in the initial period of your treatment, the doctor will have you check for 3 to 6 months after the start of treatment with a bisphosphonate for the amount of serum alkaline phosphatase in your blood. Paget’s disease of bone can remain calm for a long time after a treatment, but if you experience more pain, the bone disease may become active again. Then a new treatment with a bisphosphonate is possible again.
If you use a bisphosphonate and you have a treatment at the dentist, jaw problems can develop or worsen, such as when pulling a tooth. Always tell your dentist that you are taking a bisphosphonate and also report the dental treatment to your doctor.
Your doctor may prescribe an oral bisphosphonate medication:
• alendronate (Fosamax) or etidronate (Didronel) to be taken by mouth every day for six months.
• tiludronate (Skelid) to be taken by mouth every day for three months.
• risedronate (Actonel) to be taken by mouth every day for two months.
All oral medications should be taken with a large glass of water (6-8 oz) upon arising in the morning. Patients should remain upright for the next 30 minutes and should not eat, drink or take other medications until that time has passed. Any of these treatments can be repeated if necessary. Side effects of these medicines may involve heartburn and sometimes increasing bone pain for a short period of time.
The doctor can also prescribe injectable medications. Recent research has indicated injections may provide longer suppression of disease activity. Injectable medications that can be given for Paget’s include:
• pamidronate (Aredia), which is injected in the vein once a month or once every few months. The injection takes a few hours. Unusually, there can be inflammation of the eye or loss of bone around the teeth (osteonecrosis).
• zoledronate (Reclast), which is injected in the vein once a year. The injection takes less than 30 minutes.
• Calcitonin is a hormone found in the human body that helps with bone metabolism and calcium regulation. As hormone in the human body Calcitonin can slow bone loss in the spine and increase spine bone density. Calcitonin may also help reduce the risk of spine fractures or help decrease the pain of these fractures.
Calcitonin reduces calcium levels in the blood by two main mechanisms: it inhibits the activity of osteoclasts, which are the cells responsible for breaking down bone. When bone is broken down, the calcium contained in the bone is released into the bloodstream. Therefore, the inhibition of the osteoclasts by calcitonin directly reduces the amount of calcium released into the blood. However, this inhibition has been shown to be short-lived. It can also decrease the resorption of calcium in the kidneys, again leading to lower blood calcium levels.
Manufactured forms of calcitonin have, in the past, been given to treat Paget’s disease of bone and sometimes hypercalcaemia and bone pain. However, with the introduction of newer drugs, such as bisphosphonates, their use is now very limited. When used, calcitonin is injected under the skin several times a week. It is given as a nasal spray or as an injection.
Occasionally surgery is needed to help arthritis caused by the bone changes of Paget’s disease and can be helpful in reducing pain and improving function. Replacement of a joint can help against the pain and can improve your mobility. Medical treatment is not expected to correct some of the changes of the Paget’s disease of bone that have already occurred, such as hearing loss, deformity or osteoarthritis.
Use of drugs and adherence
• It is important that you take the drugs as prescribed. In order to get your illness under control, it is very important that you take your drugs on a regular basis every day. If you do not, there is no good concentration of the drug in your blood and therefore the drug will work less well.
• Do you have trouble remembering when and how many of your drugs you should take on a daily basis and at what time of the day? Then buy a drug dispenser, in which you can sort your drugs per day.
• Do you have difficulty or objection to taking the drug prescribed to you, for example because of possible side-effects? Then that can lead to you no longer taking the drug regularly. Discuss this with your doctor!
Deterioration of your illness and/or complications
The doctor will look at:
• The dosage and amount of drugs you use.
• Switching to another drug in the same type or a completely new type of drug.
• Combining different drugs at the same time.
Your doctor can tell you
• whether the drug can work for you.
• how you can best use the drug.
• how much and how often you can use the drug.
• how you can best reduce the drug.
You should always tell your doctor or specialist
• if you use other drugs (bought or prescribed by another doctor).
• if you have another medical condition.
• whether you will be operated on soon.
• if you have previously been prescribed an anti-inflammatory analgesic that has caused side-effects.
• whether you want to become pregnant or are pregnant.
• if you are breast-feeding.
This is important because your doctor or specialist has to make a careful choice between different drugs.
• All drugs may have side-effects when used, so ask your doctor or pharmacist what side-effects you can expect or read the leaflet.
Reduce or stop
• If you stop using a drug yourself or reduce the number of drugs yourself, your symptoms may worsen. Always consult your doctor or specialist first if you want to use less drugs or want to stop.
There are many types of alternative treatments. This refers to all treatments that fall outside normal scientific medical care. No scientific evidence has been provided for the operation of these treatments. The alternative treatments are also called ‘complementary‘ because they can supplement the regular medical treatment by your doctor.
Many people choose an alternative treatment in addition to their regular medical treatment. They hope that this helps extra against their complaints or better helps to deal with the complaints.
Can an alternative treatment be a replacement for your regular medical treatment?
No, if you opt for an alternative treatment method, it is always a supplement to your regular medical treatment. You should not stop your regular treatment, because otherwise you run unnecessary health risks. Always consult your attending doctor before you start an alternative treatment.
What alternative treatments are there for example?
There are many different alternative treatment methods available, which can also be combined. Some examples are:
• Chinese medicine (acupuncture, pressure point massage, nutrition and tai chi).
• homeopathy (products made from plants and minerals).
• Bowen therapy.
• Bach flower treatment.
• shiatsu, foot-sole and classic massage.
• Touch for Health.
• dietary supplements.
What do you have to pay attention to?
• Many alternative treatments have not shown that they actually work. If you choose to try alternative treatment, make sure that your complaints do not increase. Stop an alternative treatment as soon as your symptoms increase.
• Always consider first why you want to follow an alternative treatment.
• Prepare yourself by looking up and reading information about the alternative treatment. Consult with your attending doctor, because certain complaints may be reduced by some alternative treatment methods.
• Determine yourself in which alternative method you trust for the relief of your complaints and whether you want to start.
What can you do best when choosing an alternative treatment?
• Always consult your doctor about the alternative treatment method you want to follow.
• Consult with your attending doctor and with the alternative therapist if they want to discuss your treatment with each other.
• Choose an alternative therapist who has followed a recognized vocational training and is affiliated to a professional organization.
• Ask your alternative therapist in advance about the purpose, duration, costs and risks of the treatment. How much money you spend depends on which treatment you choose and how long it takes.
• Do not stop your regular medical treatment, as this may worsen your symptoms.
• Weigh during treatment whether you want to continue or stop if your symptoms get worse, if you do not notice any effect of the alternative treatment or if you get side-effects.
Why is your food important?
• Healthy nutrition is important to get the vitamins and minerals and other nutrients that your body needs.
• Obesity creates risks for your health and disease progression. In the case of arthritis and obesity, for example, obesity plays an important role in overburdening and osteoarthritis in the knees, hips and ankles. The pressure on your joints is then simply too great. Healthy eating and exercise (exercising a sport and active in the home and outdoors) can help to reduce or prevent excess weight.
• A healthy diet is always important and the dietitian can support you with the right dietary advice.
What is a healthy diet?
With a healthy diet your body gets the right amount of good nutrients, which it needs. You eat the quantities that your body needs. The dietitian can support you with the right nutritional advice.
The 5 courses to choose from are:
• Vegetables and fruit
• Bread, cereal products and potatoes
• Fish, legumes, meat, egg, nuts and dairy
• Lubrication and preparation fats
Where can you get advice for a healthy diet?
• You can request advice from your doctor or a dietitian. The doctor can refer you to a dietitian. Some diets may possibly help against your symptoms. Consult with your doctor or dietitian if you want to try a certain diet. And make sure that you do not omit important foods from your daily diet.
What can you do with a painful or dry mouth?
Sometimes you can suffer from a dry or painful mouth for various reasons, also due to your illness. Tips:
• by chewing (for example piece of cucumber, sugar-free candy or chewing gum) and sucking (ice cube) the salivary glands are stimulated to produce saliva.
• good oral care is important: good tooth brushing, flossing and the use of mouthwash.
• rinse your mouth regularly, drink small amounts of water and use a mouth sprayer if necessary.
• let hot drinks cool down first.
• use ice or cold dishes, because the cold numbs the pain.
• do not use sharp herbs and spices, fruit juice, carbonated soft drinks, alcoholic beverages, very salty foods and sour food.
• food with hard crusts, nuts, bones and bones can cause injuries.
• use soup, gravy or sauce with the hot meal to make the food smoother.
• spreadable cheese, spreadable paté or salad, jam or honey on bread, porridge, drinking breakfast and custard, for example, swallows easier than dry spreads.
• if you need to use ground or liquid food, you can use a mixer to grind your meal with some extra moisture.
In some forms of arthritis or use of certain drugs intestinal complaints can occur. The intestinal complaints can arise from the influence of certain drugs on food intake. Conversely, the food you eat can have an effect on the way your drugs work.
Dietary supplements, fish fatty acids, glucosamine and vitamin D?
• Dietary supplements are available as pills, powders, drops, capsules or drinks and are intended as a supplement to inadequate daily nutrition. They contain vitamins, minerals or bio-active substances. These synthetic or isolated vitamins, minerals or bio-active substances have the same effect as the vitamins and minerals that are already naturally in your food and drink.
Many people choose an additional supplement, in addition to their daily diet. The users of dietary supplements indicate that they experience positive effects of the use of certain herbs, vitamins and minerals. The body absorbs the nutrients in pills more easily than the nutrients in food. But if you eat healthy and varied, you do not need additional nutritional supplements, because you already get enough nutrients, minerals and vitamins. Always report to your doctor and pharmacist that you are using dietary supplements.
• Fish fatty acids appear to have a mild anti-inflammatory effect with a high intake. Research has been done especially in rheumatoid arthritis. The advice is to eat oily fish twice a week.
• Glucosamine can act as a mild painkiller for osteoarthritis in the knee, but does not stop arthritis.
• Our body naturally makes vitamin D under the influence of outdoor sunlight. Vitamin D may have a beneficial effect in inflammatory arthritis, but that has not yet been proven sufficiently. People with Lupus erythematosus get vitamin D prescribed as they are not often outside, because sun exposure can lead to lupus flares and skin problems. Vitamine D is given with calcium tablets to ensure a good intake in the body, when you have osteoporosis or osteoarthritis.
Living with Paget’s disease of bone
With Paget’s disease, it is the fast bone rebuilding that leads to complications such as bone pain, enlarged head, bowed arms or legs, arthritis (osteoarthritis), back pain, loss of hearing, broken bones (fractures), heart failure and, rarely, a form of bone cancer.
Regular exercise is good, because it keeps joints supple, makes muscles, heart and lungs stronger, prevents bone loss, reduces your fat percentage, lowers cholesterol levels and improves your overall body condition.
• Pay attention to your excess weight or obesity.
• Eat healthy food, vegetables, fruit and so on.
• Keep moving: by walking you remain flexible and in good condition.
• Practice daily with your painful or stiff joints. A physiotherapist can give you exercises.
• Ensure that your home and workplace have a pleasant temperature. Avoid large temperature differences.
• Protect your joints against cold.
• Pay attention to your posture: a bad posture is an extra heavy load for your body.
• Change your posture regularly: do not sit, stand or lie in the same position for too long.
• Alternate movement and rest.
• Avoid climbing stairs or squatting, crawling and kneeling too much.
• Do not lift or carry heavy things.
• Use tools on time. Do not wait until you cannot do anything anymore.
• Wear comfortable shoes with sturdy soles that do not pinch and give enough support when walking.
Amgen I Introduction to Bone Biology
Amgen I Osteoblasts and Osteoclasts
Amgen I Bone Remodeling and Modeling
Amgen I Regulation of Osteoclast Activity
Amgen I Sclerostin
Amgen I Anatomy of a Fracture as a Result of Systemic Bone Loss
Intelecom Learning I Development of Bone
Amgen I Introduction to Bone Biology I https://youtu.be/inqWoakkiTc
Amgen I Osteoblasts and Osteoclasts I https://youtu.be/78RBpWSOl08
Amgen I Bone Remodeling and Modeling I https://youtu.be/0dV1Bwe2v6c
Amgen I Regulation of Osteoclast Activity I https://youtu.be/GpMV197xZXc
Amgen I Anatomy of a Fracture as a Result of Systemic Bone Loss I https://youtu.be/P5HwYWShBhw
Amgen I Sclerostin I https://youtu.be/ajsioxRrf1I
Intelecom Learning I Development of Bone I https://youtu.be/xXgZap0AvL0
Accountability text Paget’s disease of bone
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