Scientist Reveal What Cannabis Does to Your Bone


A study from the Hebrew University and Tel Aviv University showed how a chemical in marijuana has strengthening effects on bone. The chemical is cannabinoid cannabidiol (CBD) and fastens bone healing without any psychotropic effects. This study was published in The Journal of Bone and Mineral Research.

 Researcher Yankel Gabet said that treatment of bones with CBD ensures strong, healed bones that will not break easily. It will help the maturation of collagenous matrix, which provides a new base for materialization of bone tissue.

The researchers used rats for this study by causing mild femoral fractures in them. They injected CBD to some of them, while the rest received CBD and tetrahydrocannabinol, which causes the marijuana high. They compared the two effects and found that rats injected with CBD showed the same results immaterial of THC addition.

The researchers also found that receptors in the body which react to cannabinoid compounds are not just located in the brain but are in the bones too. This helps the creation of bones and stops bone loss.

This study is a part of a project to find marijuana’s medical benefits and these new discoveries might motivate researchers to find the benefits of marijuana in treating osteoporosis and other bone diseases.

Gabet said that our body reacts to cannabis because we have receptors and compounds that are activated by compounds in marijuana.

These developments definitely show that cannabis has undeniable medicinal properties and that they can separate the clinical possibilities from the psycho-activity of cannabis.

Cannabis has several medicinal properties. AIDS patients use it to increase their appetite or to reduce side-effects of chemotherapy and chronic pain. Many studies show that it can regulate blood sugar and help in the treatment of multiple sclerosis and Parkinson’s disease.

The study also reveals that CBD controls seizures, prevents metastasis of aggressive cancers and destroys leukemia cells.

Neuropsychopharmacology published a study that stated CBD is as beneficial as an antipsychotic drug. CBD is able to treat schizophrenia and paranoia, without any side-effects.

Although illegal under U.S Federal law, 17 states permit the use of CBD for research and medical purposes. Laws of 23 other countries also allow the use of marijuana for medicinal functions.

The federal government still doesn’t recognize marijuana as an “accepted medical use”. However, the recent FDA approval of CBD extracts in an experimental treatment for the Dravet syndrome.

Depression Hurts, Your Bones Included


Growing evidence suggests that depression, one of the most common diseases of the brain, is so powerful it can actually erode bones in the body.

Depression Hurts, Your Bones Included

Our bones are constantly remodeling themselves – they build themselves up and break themselves down over and over again. Depression is like a severe and prolonged state of stress on bones that may weaken them, making osteoporosis more likely. Depression causes blood pressure and heart rate to increase and also causes the brain to produce dangerously high levels of hormones – it has also been suggested that specific hormonal changes associated with depression lead to bone loss.

Depression not only affects your brain and behavior—it affects your entire body, and that includes your bone health and risk of developing osteoporosis.

Someone suffering from depression might experience bouts ofinsomnia, loss of appetite, and overall lethargy, and these are all contributors to poor bone health. Studies show that older people with depression are more likely to have low bone mass than older people who aren’t depressed, and low bone mass is the biggest indicator of osteoporosis.

Younger women with depression may also be at risk for osteoporosis. One study found that among women who have not yet reached menopause, those with mild depression have less bone mass than those who aren’t depressed. Men who are depressed seem to lose bone even more rapidly and to a greater extent than women, however since bone density in men is greater to begin with, their risk of fracture may be slightly more forgiving than in women.

Medication

While currently available depression treatments are generally well tolerated and safe, some medications, including some antidepressants, anticonvulsants, and lithium, can increase your risk for osteoporosis. Certain medications can also increase your risk of falling, which is dangerous if you already have osteoporosis. The class of antidepressants known as SSRIs may be associated with higher rates of bone loss in older women.

A recent study funded by the NIH showed an association between SSRI use and hipbone loss in older women. In patients with depression and those on SSRIs, attention should be directed to the heightened risk of fragility fracture – a broken bone that’s caused by a fall from a standing height or less, indicating an underlying bone disorder like osteoporosis.

Lifestyle

If you have osteoporosis, you may need to make lifestyle changes, and these changes may actually increase your risk of depression. For example:

– To prevent falls that could cause already fragile bones to fracture or break, you may not be able to take part in some activities you once enjoyed.
– Weakened bones may make it harder to perform everyday tasks, and you could lose some of your independence.
– You may feel nervous about going to crowded places, such as malls or movie theaters, for fear of falling and breaking a bone.

But it can go the other way, too. Exercise is an important part of osteoporosis treatment, particularly activities in which you support your weight on your feet. These activities help to strengthen bones and muscles that can prevent falls and can also boost your mood and improve your depression.

People with depression and low bone mass need to try very hard to adopt bone health strategies, including use of supplements, quitting smoking, limiting alcohol consumption to fewer than two glasses a day, and participating in weight-bearing exercises and fall-prevention programs. Because earlyosteoporosis is primarily a silent disease, knowing that even mild depression can lead to bone loss years before fractures occur is of major clinical importance. Orthopedic surgeons should be aware of the association between depression and osteoporosis as well as the higher rate of bone loss in patients on SSRI medication for their depression. Treating depression can help you manage your osteoporosis and improve your overall health. Recovery from depression takes time but treatments are effective.

Metastatic Disease to Bone .


Watch the video. URL: https://youtu.be/7czbkvd2ruk

 

7 metastatic disease of boneJ

Do You Really Need a Vitamin D Supplement?


A new study says that taking vitamin D supplements for bone-strengthening and protection against osteoporosis is not necessary for healthy middle-aged adults.

But a bone health expert at Cleveland Clinic urges people at risk for vitamin D deficiency to consult their doctors before discontinuing use.

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Studies showed no significant increase in BMD

Recent concerns about the safety risks of taking calcium supplements has led some adults to take vitamin D (without calcium) for bone protection.

The University of Auckland study — a meta-analysis of past studies — found that vitamin D supplements alone had little effect on bone-mineral density (BMD). Investigators combined data from 23 past trials, studying 4082 adults, 92 percent of whom were women. Studies showed no significant increase in BMD in most areas of the body.

In light of this researchers concluded that widespread use of vitamin D for osteoporosis prevention in adults without risk factors for vitamin D deficiency was unwarranted.

Importance of vitamin D shouldn’t be minimized

Chad Deal, MD, was not involved in the study but is Director of the Center of Osteoporosis and Metabolic Bone Disease at Cleveland Clinic.

Though not disagreeing with the study’s conclusions, he worries that the findings may cause some to minimize the positive impact of vitamin D on at-risk people.

“The study is on the effect of vitamin D on BMD, which is modest and not surprising,” says Dr. Deal. “Vitamin D would not be expected to have a large effect unless the patient had severe vitamin D deficiency, in which case the bone density effect could be significant.”

“Patients with vitamin D deficiency should not get the take-home message that vitamin D will not benefit them,” he says.

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Fracture protection and other safeguards

For older, at-risk patients, vitamin D deficiency can have a major impact on fracture, says Dr. Deal. Deficiency can cause osteomalacia, softening of the bone due to impaired mineralization, which makes fractures more likely.

Bone mineral density is not a perfect surrogate for fracture, especially in older patients,” Dr. Deal says.

Vitamin D can also have “huge benefits” on muscle function, cognition and falling, he adds.

Healthy middle-aged adults should talk to their doctor about both their vitamin D and calcium levels to see if they need to be taking vitamin D supplements, either alone or with calcium.

A Bio-Patch Regrows Bone Inside the Body.


Researchers from the University of Iowa have developed a remarkable new procedure for regenerating missing or damaged bone. It’s called a “bio patch” — and it works by sending bone-producing instructions directly into cells using microscopic particles embedded with DNA.

In experiments, the gene-encoding patch has already regrown bone fully enough to cover skull wounds in test animals. It has also stimulated new growth in human bone marrow stromal cells. Eventually, the patch could be used to repair birth defects involving missing bone around the head or face. It could also help dentists rebuild bone in areas which provides a concrete-like foundation for implants.

To create the bio patch, a research team led by Satheesh Elangovan delivered bone-producing instructions to existing bone cells inside a living body, which allowed those cell to produce the required proteins for more bone production. This was accomplished by using a piece of DNA that encodes for a platelet-derived growth factor called PDGF-B. Previous research relied on repeated applications from the outside, but they proved costly, intensive, and more difficult to replicate with any kind of consistency.

“We delivered the DNA to the cells, so that the cells produce the protein and that’s how the protein is generated to enhance bone regeneration,” explained Aliasger Salem in a statement. “If you deliver just the protein, you have keep delivering it with continuous injections to maintain the dose. With our method, you get local, sustained expression over a prolonged period of time without having to give continued doses of protein.” Salem is a professor in the College of Pharmacy and a co-corresponding author on the paper.

While performing the procedure, the researchers made a collagen scaffold in the actual shape and size of the bone defect. The patch, which was loaded with synthetically created plasmids and outfitted with the genetic instructions for building bone did the rest, achieving complete regeneration that matched the shape of what should have been there. This was followed by inserting the scaffold onto the missing area. Four weeks is usually all that it took — growing 44-times more bone and soft tissue in the affected areas compared to just the scaffold alone.

“The delivery mechanism is the scaffold loaded with the plasmid,” Salem says. “When cells migrate into the scaffold, they meet with the plasmid, they take up the plasmid, and they get the encoding to start producing PDGF-B, which enhances bone regeneration.”

Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives.


Glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, the therapeutic use of glucocorticoids is almost always limited by substantial adverse outcomes such as osteoporosis, diabetes, and obesity. These unwanted outcomes are a major dilemma for clinicians because improvements in the primary disorder seem to be achievable only by accepting substantial adverse effects that are often difficult to prevent or treat. To understand the pathogenesis of glucocorticoid-induced osteoporosis, it is necessary to consider that the actions of glucocorticoids on bone and mineral metabolism are strongly dose and time dependent. At physiological concentrations, endogenous glucocorticoids are key regulators of mesenchymal cell differentiation and bone development, with additional regulatory roles in renal and intestinal calcium handling. However, at supraphysiological concentrations, glucocorticoids affect the same systems in different and often unfavourable ways. For many years, these anabolic and catabolic actions of glucocorticoids on bone were deemed paradoxical. In this Review, we highlight recent advances in our understanding of the mechanisms underlying the physiology and pathophysiology of glucocorticoid action on the skeleton and discuss present and future management strategies for glucocorticoid-induced osteoporosis.

Source: Lancet

 

 

 

Bone is a plastic tissue .


Decades ago, medical school final exams took the form of essays rather than the current multiple choice questions. For the histology finals, I selected the topic “Bone is a plastic tissue.” I knew absolutely nothing about the skeleton other than it was brittle and broken. It turns out that not only was I wrong but I knew as little about it as the professors: for the one and only time in medical school, I topped the class.

Bone is clearly a plastic tissue subject to modeling during growth and development and remodeling shortly after epiphyseal closure. The most common skeletal disease resulting from altered remodeling is osteoporosis in which resorption outstrips formation. Monitoring resorption and formation — measures of total skeletal metabolism — is overlooked in favor of monitoring bone mineral density — measures of regional, not total, skeletal status.

Why bring this up now?

A PubMed search for the last 10 years returned 35,121 citations (275 meta-analyses) for “bone density” and 13,162 citations (28 meta-analyses) for “bone turnover markers”. There is clearly no shortage of peer-reviewed literature regarding bone turnover markers, but there is so much variability in those 13,162 citations that meaningful consensus data is lacking.

You don’t need reminding that adherence to oral medications for osteoporosis is low, and not that great for injectable (subcutaneous or IV) therapies. Several studies have examined the use of markers to improve medication adherence but, to my knowledge, none of them have found markers to be useful in maintaining compliance with therapy.

Bone turnover markers have no role in determining which patient is a candidate for osteoporosis therapy and have not had much effect on patient adherence to therapy. My own practice is to measure markers as I recommend the patient start therapy and re-check markers after 6 months of therapy to both monitor that the therapy is effective and that the patient is adherent to therapy. My success rate in the latter is no better than reported in the literature.

I repeat measurement of markers when serial measurement of BMD indicates that BMD is no longer increasing. Ongoing use of osteoporosis therapies is safe for the vast majority of patients in whom BMD has plateaued, but there is increasing awareness of atypical femoral shaft fractures in a small minority of patients on long-term antiresorptive therapy. With that in mind, I interrupt therapy in patients with stable BMD, where bone turnover markers are in the bottom quartile of the reference interval. I re-check them at 6 monthly intervals until the values get to the top half of the reference interval, at which time therapy is re-started. That happens infrequently. When allowed by insurance coverage, I repeat BMD measurement after 1 year off therapy but have yet to see a patient in whom BMD has declined during that year. I cannot recall a patient in whom an uptick in remodeling has not occurred within 2 years without antiresorptive therapy and use that as an indication to re-start treatment.

Which markers to use? My preference is or serum CTX (resorption) and P1NP (formation) because patients are never in a hurry to provide a 24-hour urine collection or even a fasting urine sample.

Much has been written about the diurnal variation of biochemical markers of bone remodeling and the intra- and interassay variability. These are specious arguments against serial measurements of bone turnover markers. Firstly, when remodeling is suppressed as a result of therapy, even 50% variability in markers (it is not that variable) does not move many patients from one quartile to another. Secondly, there are many laboratory tests in which the variability is the same or even worse than for bone turnover markers. That has not stopped any clinician I know from continuing to order and rely on those results.

The bottom line — patient adherence to therapy tests our skills as clinicians every day. Asking a patient to wait 2 years to see if the therapy we prescribe is effective or not makes little sense to me.

Michael Kleerekoper, MD, MACE, has joined the faculty at the University of Toledo Medical School where he is Professor in the Department of Internal Medicine and section chief of the Endocrinology Division. The author of numerous journal studies, Dr. Kleerekoper serves on the editorial boards for Endocrine Today, Endocrine Practice, Journal of Clinical Densitometry, Journal of Women’s Health, Osteoporosis International and Calcified Tissue International. Dr. Kleerekoper is also a founding board member of the newly formed Academy of Women’s Health.

Source: Endocrine Today.

 

Expansile, lytic and hypermetabolic bone lesions not always metastatic cancer .


A 44-year-old man was referred for evaluation of hypercalcemia. He had atraumatic rib and clavicle fractures in the setting of marked hypercalcemia and symptomatic nephrolithiasis.

His medical history included chronic kidney disease due to obstructive bilateral hydronephrosis and coronary artery disease requiring multiple percutaneous coronary interventions. His symptoms, consistent with hypercalcemia, included polyuria, nocturia, malaise, muscle weakness, depression and early morning nausea. He had no family history of endocrine disease. Physical examination was remarkable for widespread nonspecific bony tenderness on deep palpation. Proximal muscle weakness was prominent, including an inability to rise from a crouched position or walking up a step without aid. Thyroid and neck examination were unremarkable.

His serum calcium levels ranged from 10.9 mg/dL to 13.3 mg/dL during the previous year, with corresponding intact parathyroid (PTH) between 3,111 pg/mL and 4,023 pg/mL. His 25-hydroxyvitamin D level was 23 ng/mL. Serum phosphorus level was suppressed to 2 mg/dL, and serum creatinine trended up from 1.5 mg/dL to 2.2 mg/dL.

His markers of bone turnover were very elevated, with an alkaline phosphatase of 1,344 units/L (reference: 25-100 units/L), spot urinary N-telopeptide of 311 nmol/mmol (reference: 9-60 nmol/mmol) and serum osteocalcin .300 ng/mL (reference: 9-38 ng/mL).

Extensive imaging studies were performed for the presumed diagnosis of pathological fractures. An 18F-fluorodeoxyglucose (FDG) PET/CT scan revealed hypermetabolic lesions corresponding to expansile and lytic regions in multiple ribs, vertebral bodies, iliac bones, pubic rami, acetabulum and right clavicle (Figures 1 and 2). Axial DXA bone mineral density scan showed osteopenia at both the lumbar spine (T-score –2.2) and femoral neck (T-score –2.2), and the distal radius showed marked bone loss (T-score –6.9) demonstrating preferential cortical bone loss from hyperparathyroidism (HPT). A bone biopsy of one of the larger lesions was performed with pathology consistent with osteitis fibrosa cystica (OFC).

A diagnosis of primary HPT was established with elevated PTH and calcium levels with nephrolithiasis, chronic kidney disease, osteoporosis and OFC with pathological multisite fractures.

Initial 99-technetium sestamibi PTH scan at an outside hospital was non-localizing, but when repeated with mediastinal views, abnormal uptake in the anterior mediastinum was seen, consistent with a 5-cm mediastinal PTH adenoma or carcinoma.

OFC was once the dominant clinical manifestation of primary HPT. With modern improvement in laboratory testing and early diagnosis, OFC has become exceedingly rare but is still seen in the developing world. Friedrich Daniel Von Recklinghausen is credited with describing the first case of OFC in 1891; however, the association with parathyroid disease was noted by Askanazy in 1904. OFC is also known as Recklinghausen’s disease of bone. The more severe cystic changes seen in OFC have been termed “brown tumors.” Histologically, these “tumors” are highly vascular and are composed of clusters of giant cells in a background of mononuclear or spindle cells with hemosiderin. OFC is characterized by PTH-mediated increase in osteoclast activity, peritrabecular fibrosis and “tunneling” resorption of trabeculae, which leads to the cystic changes and expansile, lytic features noted on imaging.

Cortical, rather than trabecular, bone loss is more prominent due to the anabolic effect of PTH on trabecular bone. However, in severe long-standing cases, trabecular bone is not spared and osteoporosis at axial skeletal sites is common. In severe forms of the disease, marked skeletal deformity, minimal trauma fractures and bony pain may result in severe disability. Primary HPT with osteoporosis or OFC would warrant surgical resection of the parathyroid adenoma, given the risk for progressive bone remodeling, fractures and potential skeletal deformity.

A case series of 51 patients in India with primary HPT and OFC were followed after parathyroidectomy with an intention to measure bone recovery postoperatively. BMD recovery was impressive and occurred early (within 1 week) and was more prominent in trabecular bone than cortical bone sites. Bone pain improved in 71% of patients. Despite improvements in BMD after surgery, re-mineralization was not universal at all bone sites and many patients never regained normal BMD after 4 years of follow-up. Brown tumors and skeletal deformity improved overall; however, radiological deformity persists and may require corrective surgery.

OFC is an increasingly uncommon presentation of primary hyperparathyroidism. The diagnosis should be suspected in patients with pathological fractures and hypercalcemia. Appropriate surgical removal of the causative parathyroid tumor has early and positive benefits on bone health, but the most severe form of HPT osteodystrophy, brown tumors or OFC, may not structurally return to normal and continue to be at an increased risk for fracture.

References:
  • Agarwal G. Surgery. 2002;132:1075-1083.
  • Kearns AE. Mayo Clin Proc. 2002;77:87-91.
  • Pai M. Clin Nucl Med.1997;22:691-694.

 

Source: the Oncologist.