MORE ON BONES

The Five Pillars of Feline Welfare

The sun shone for us on our Scott Creative Arts Foundation and Living Landscape Community Project Open Day and a great day was had by artists, garden volunteers and visitors. Big thanks go to Heck! for the loan of their bright pink minibus, which allowed us to ferry people to and from Thirsk centre throughout the day, Mouse for the loan of his amazing sculptures, Aquatic Finatic who valiantly stood in for our missing alpacas, George the chilled DJ, the HorseBox Pizza Company for delicious food and to Betty’s of Harrogate for the super hamper as our raffle prize! The months of planning and preparation are now over and we look forward to welcoming artists and visitors to the SCAF Emerging Artist Award Exhibition over the next month. Free runner beans with every visit is a distinct possibility despite the drought!

So now back to bones and what we can do to diagnose, treat and ideally prevent osteoporosis. This is going to be directed at humans, however, if osteoporosis is recognised in animals, the treatment options currently would be similar.

Many of you will be familiar with the term DEXA or bone density scan as this is currently offered by the NHS to those deemed to be at risk. The DEXA or dual-energy X-ray absorptiometry scan, measures bone density at fixed levels of the lower spine and hips, to allow comparison with reference scans and over time to monitor disease progression and response to interventions. MRI, quantitative computed tomography (QCT) and ultrasound have all been explored to diagnose the condition but are less frequently used.

In addition to imaging there are several biomarkers that are useful such as those that indicate bone turnover e.g. c-terminal telopeptide (CTX) and n-telopeptide (NTX) as well as levels of blood osteocalcin (a vitamin K dependent protein produce by bone-forming osteoblasts) and sclerostin (secreted by osteoclasts that are negative bone regulators). General assessment of inflammatory markers can also be useful as well as looking at oestrogen and testosterone levels of patients. For the more rare forms of osteoporosis genetic testing for some of the known gene mutations can also be performed to support diagnosis.

When it comes to treatment the entry level supplement has always been calcium, however, if taken on its own it is simply not enough and in excess can even increase fracture risk! It doesn’t take a genius to work out that postmenopausal women do not suddenly become calcium deficient for no reason, when they are eating exactly the same diet they have eaten for fifty years or more! It is the bodies ability to take that calcium up into the bone that changes as the hormones change and not the level of calcium in the diet that suddenly decreases, thus whilst ensuring that we all take in adequate levels of calcium in our diet, merely supplementing with calcium alone will never fix this problem.

The emphasis has to be directed towards supporting uptake of calcium and phosphorous and other cofactors into the bone i.e. supporting osteogenesis. Vitamins D3 and K2 are essential cofactors to aid calcium uptake into bone and should therefore be taken with any calcium supplement. Other nutrients such as vitamin C, magnesium and flavonoid polyphenols may also be beneficial for bone health. Plant polyphenols such as quercetin, rutin, luteolin, kaempferol and naringin have been shown, both in vitro and in vivo to positively affect bone microstructure and biochemical parameters. Not only do they show positive effects on bone health but they can also delay the aging process and reduce the incidence of many chronic diseases such as type 2 diabetes, cataracts and cognitive impairment. These can either be taken in supplement form but also as a vital part of a varied diet as these are all found in certain edible plants and vegetables. Quercetin for example is found in onions, red leaf lettuce, tomatoes, peppers and asparagus, to name but a few of the rich sources of this important phytonutrient. Many of these polyphenols have been shown to act in post menopausal individuals in the face of diminished oestrogen levels, for example quercetin is able to bind to oestrogen receptors and affect the activity of osteoblasts and osteoclasts, as well as altering the expression and activity of various inflammatory cytokines involved in bone remodelling.

In addition to specific supplements, more general dietary considerations are of paramount importance as humans age. Maintaining adequate protein intake is essential to skeletal health. Protein forms a large component of bone matrix, it regulates blood levels of insulin-like growth factor 1 (IGF-1) and may affect calcium metabolism. As well as protein intake, ensuring an adequate intake of Polyunsaturated fatty acids (PUFAs), found in seafood and fish oil supplements has also been shown to decrease fracture risk by helping to maintain higher bone mineral density (BMD).

Diet therefore, with or without the addition of nutritional supplements, as well as daily weight bearing exercise and muscle strength training are all things we can do to address both prevention and support our bone health and yet the information given to patients by the medical profession rarely mentions such simple things in my experience of the thousands of patients I have treated over the years.

Traditional therapeutics in the UK usually starts with Calcium and Vitamin D and then goes on to the bisphosphonates, followed by denosumab and anabolic agents such as teriparatide and romosozumab in more severe refractory cases. These drugs have a place (and are increasingly being prescribed) but can come at a cost. The first bisphosphonate (Alendronate) used in the UK is in an oral form that frequently causes gastrointestinal issues such as nausea, dyspepsia and abdominal pain and needs to be taken daily, standing upright for half an hour after taking it with water, to try and avoid damage to the oesophagus! A second major issue with all bisphosphonates is that they lower calcium levels, yes I did say lower! This can lead to bone fragility and fractures through brittle bones and in rare cases to osteonecrosis of the jaw (ONJ) and subsequent jaw fractures. They can also affect kidney function and produce inflammation in the eyes e.g. uveitis, conjunctivitis, in some patients. Whilst the daily oral form can be stopped quickly, the longer acting infusion form bisphosphonates cannot be reversed, which can be a major issue for those suffering from significant side effects. Denosumab sadly has a similar if not worse side effect profile, but is now being used in severe cases where other medications have not been working.

Stem cell therapy and gene editing technologies are showing some promise in the research world for future treatment of osteoporosis. CRISPR/Cas9 has the potential to correct for example mutations in COL1A1 and COL1A2 genes, which encode type 1 collagen, a common cause of osteogenesis imperfecta, a rare form of osteoporosis. There is a long way to go with these technologies but I have no doubt that they will be become part of the conventional therapeutic landscape in years to come, at least for those that can afford it.

If we look around the world at the incidence rates of osteoporosis, the levels are significantly higher in Africa and Europe compared to Asia. There are likely to be multiple potential differences that will be involved in explaining the disease expression differences between the continents, but I am sure that we do not have it right in the west and we need to rethink this disease and our approach to its prevention and treatment.

The Five Pillars of Feline Welfare

Currently, approximately 10.5 million pet cats live in the UK (approximately 25% of households) and 73.8 million in the USA. Cat ownership is believed to be increasing at a greater rate than dog ownership partly as a consequence of the trend for people to live in ever smaller spaces in urban areas. The cost of pet ownership, added to the ever increasing cost of living, is another important factor both in terms of time and money, making cat ownership the more affordable option for many. Cats, however, are not simply a cheaper version of dogs that don’t need walking. Maybe obvious to most of you reading this article, but not so for a growing number of people who make the decision to get a cat and come to regret it, often due to problem behaviours that with a little help could have been avoided.