From speaking with our community of practitioners, we learnt that many wanted handy reference guides to summarises advanced testing options for key health conditions.
In light of this, our Clinical Support Specialist, Virginia Blake, has written a clinically robust introduction to advanced testing options for Osteoporosis..
Read and bookmark this page if ever you are looking for a starting point for advanced testing options for osteoporosis.
Lesson objectives:
- To classify osteoporosis
- To summarise osteoporosis' key risk factors
- To provide a summary of the advanced functional tests avaliable to practitioners to assess and manage osteoporosis
Epidemiology
Osteoporosis is more common in women (5%) than men (1%) with risk increasing with age. Lifetime estimates for osteoporotic fracture are a 50% risk in women and a 20% risk in men. (Clynes et al., 2020) Incidence of osteoporosis is considered to be increasing. Often, it is not diagnosed or treated until multiple fractures have occurred. Fractures resulting from osteoporosis are a significant cause of mortality and morbidity (Barton et al., 2019).
Classification
Osteoporosis is incurable and chronic. Skeletal integrity is compromised and there is characteristic low bone mineral density (BMD) and degradation of the bone architecture. (Brown, 2021). This results in fragility fractures. Almost 80% of fractures in post-menopausal women are osteoporosis related (Bessette et al., 2007) It is a systemic disease and can be either primary or secondary. Primary osteoporosis is the most common presentation and secondary usually occurs as side effect of certain medications (e.g. corticosteroids) or conditions (SIGN,2020).
Pathogenesis
Rates of bone resorption exceed bone formation and deposition. Increased osteoclast activity is found alongside reduced activity of osteoblasts (Aibar-Almazán et al., 2022).
Risk Factors
Non-Modifiable
Age: Risk increases post 50 with a steep rise in risk of fracture for women over 65 and men over 75.
Gender: Lifetime risk for women of osteoporotic fracture is up to 5 times greater than the risk for men. Ethnicity Caucasian men and women demonstrate greatest risk of overall fracture risk. Black Caribbean women have the lowest risk of fractures at all sites. For men, Bangladeshi men are at lowest risk for any osteoporotic fracture.
Previous fracture: A meta-analysis of 11 cohort studies (n=60,161 women and men) concluded that any previous fracture was associated with increased risk of osteoporotic fracture (RR 1.77, 95%CI) (SIGN,2020).
Family History: There is a significant association of family history and increased risk of osteoporotic fracture for women (cohort Study, n=1.2m). The evidence is conflicting in men with some studies suggesting no association (Hippisley-Cox & Coupland, 2009); and other work finding that both men and women had increased risk of osteoporotic fracture if there was family history of osteoporosis (Kanis et al., 2004).
Reproductive Factors: Both late menarche (≥16) and early menopause (≥47) not treated with HRT, increase risk of osteoporosis (SIGN, 2020)
Modifiable Risk Factors
Alcohol intake: Knowing that alcoholism is a risk factor for osteoporotic fracture, Berg et al. (2008) conducted a systematic review and meta-analysis to investigate the association between alcohol intake and fracture risk.
Lowest risk was for the group having 0.2-1.7 drinks per day compared to abstainers and those having more than 2 drinks per day. The suggested mechanism: moderate drinking increases serum oestradiol and liver oestrogen receptors and this has a beneficial effect on bone modelling. (I am always wary of studies comparing abstainers to moderate drinkers.
The abstainer population generally has people who do not drink for other health reasons that may affect bone density and also includes previous heavy drinkers who are now abstainers. Moderate drinkers generally includes people who drink at Christmas and weddings only as well as the daily tipplers, with units averaged out across the study population.)
Weight: Low Body Weight in women with normal menstruation in the absence of anorexia nervosa may have increased risk of osteoporosis. In a small study of 25 women with author described ‘constitutional thinness”; 44 women with anorexia nervosa (AN) (BMI <16.5kg/m2) and 28 age matched controls, the constitutionally thin women showed greater impairment of bone structure. AN bone structure was only affected in lengthy history of disease (Galusca et al., 2008). Similar results were also found for male adolescents with constitutionally thin boys having lower BMD compared to boys with AN (Pehlivantürk Kızılkan et al., 2018).
Smoking: Recognised in the 1980s as a risk factor for osteoporosis, there are several mechanisms linking it with reduced BMD: free radical production from harmful chemicals in cigarettes increases the production of enzymes that break down oestrogen Oxidative stress damaging collagen production Suppression of Osteoprotegerin (OPG), inhibits bone breakdown. Higher levels of receptor activator nuclear kappa-β ligand (RANKL)in smokers (which stimulates osteoclast activity. Stopping smoking increases BMD after 10 years nicotine free (Aibar-Almazán et al., 2022). Physical Inactivity Lack of exercise can lead to a reduction in BMD and in bone architecture. BMD loss can be slowed by physical exercise (SIGN, 2020).
Helicobacter Pylori: Although findings are mixed, some research suggests a strong link between H.pylori infection and osteoporosis. An association with decreased bone density in pre-menopausal women with H. pylori has been found.
Potential mechanisms include systemic inflammation caused by infection resulting in increased production of TNF-alpha, IL-1 and IL-6. These cytokines can reduce BMD. There may also be a decrease in B12 levels, absorption levels may drop when there is H.Pylori present. Lower serum B12 is associated with increasing risk of osteoporosis (Tucker et al., 2004). Increase in stomach pH may affect calcium ionisation and absorption (Wang et al., 2020). Homocysteine (HCY) Increased levels of HCY are associated with increased oxidative stress in bone. Increased levels of reactive oxygen species (ROS) promote increased apoptosis of osteoblasts, reducing osteoblastgenesis. Osteoclasts have been shown to be very sensitive to increased ROS, increasing their activity. HCY also reduces apoptosis of osteoclasts (Behera et al., 2017.
Vitamin D and Calcium: Ninety-nine per cent of the body’s stored calcium is in the skeleton and it is vital for structure of bone. It makes sense to think about a lack of calcium contributing to osteoporosis (Reid et al., 2008). The evidence on supplementation is mixed though, with some studies suggesting a benefit and some studies suggesting an increased risk of hip fracture on calcium supplements (Tang et al., 2007; Reid et al., 2008).
A small, observational study has shown increased risk of dementia with calcium supplementation in elderly women with pre-existing cerebrovascular disease (Kern et al., 2016) Later work finds that higher serum calcium levels are protective against further cognitive decline (Lin et al., 2022). I am heading off on a tangent here, but your older clients will be interested in their bones and their brains and may ask about supplementation of calcium. The answer – the evidence is unclear, but the dementia risk is unproven and the work needs to be repeated in a larger population before any conclusion is made.
Hip fractures increase with age and are linked with a loss of muscle mass and function. As well as its role in calcium homeostasis, there is evidence that vitamin D is important for normal muscle function. Vitamin D receptors found on muscle decline with age (LeBoff et al., 2008). Very low 25(OH)D (<40nmol/L) concentrations were linked with a reduced ability to walk 8 feet and complete the sit to stand test effectively. Vitamin D deficiency is common in the elderly with hip fractures (Bischoff-Ferrari et al., 2004).
Digestive Health: To absorb calcium, it must be ionised by stomach acid in the digestive system. Stomach acid secretion can be reduced in 30% of those over 65, which may affect calcium absorption (Feldman et al., 1996). Osteoporosis can be caused by inflammatory bowel disease (IBD), more commonly in Crohn’s than ulcerative colitis. Poor nutrition, malabsorption and increased inflammatory cytokines which directly affect bone metabolism are all implicated. (Piodi et al., 2014).
Heavy Metals: Higher serum levels of cadmium, lead, arsenic and mercury are associated with lower BMD and increased risk of osteoporosis. Cadmium is the most well known in this regard, with Itai-Itai (translates to ‘it hurts’) disease caused by industrial cadmium pollution in Japan (Lim et al., 2016).
Secondary Osteoporosis
- Other causes of osteoporosis:
- Gastrointestinal disease (malabsorption, post-gastrectomy)
- Glucocorticoid excess (exogenous or endogenous)
- Hypercalciuria • Hypogonadism (including androgen deprivation therapy)
- Other endocrine diseases (e.g. hyperparathyroidism, hyperthyroidism)
- Malignancy (e.g. multiple myeloma, leukaemia)
- Mastocytosis
- Rheumatoid arthritis
- Chronic obstructive pulmonary disease. (Binkley, 2009)
Relevant Testing
General Overview Tests
Functional Platinum Panel by Medical Diagnosis
The Functional Platinum Panel provides a comprehensive insight into these key health areas: full blood count, biochemistry, endocrinology, haematology, hepatology, thyroid function and immunology.
This an excellent all round test, alongside areas listed above, it also assesses vitamin B12, calcium, iron including ferritin and TIBC, folate, vitamin D and homocysteine. Thyroperoxidase and thyroglobulin antibodies are included. By analysing the liver markers, insight into bone turnover can be inferred, specifically reviewing alkaline phosphatase (ALP). ALP is found at high levels in bone, if this marker is raised in relation to other liver markers, it suggests an increased rate of bone breakdown (Vimalraj, 2020). If I could only choose one test for an osteoporotic client, this would be it.
Organic Acid Test (OAT) by Great Plains Laboratory
An evaluation of 76 biomarkers provides a comprehensive metabolic snapshot of overall health, including intestinal microbial overgrowth (yeast and bacteria), mitochondrial health, neurotransmitter status, detox capacity, oxidative stress, markers for vitamin and mineral levels and oxalates.
This is another big picture test, particularly relevant in osteoporosis as it can give a broad picture of system health.
Endocrine
DUTCH Complete by Precision Analytical
Levels of oestrogen parent hormones and metabolites would be helpful to know given the link between osteoporosis and declining sex steroids. Also includes B12 and B6 assessment.
DUTCH Plus by Precision Analytical
As DUTCH Complete above, with additional assessment of the cortisol awakening response (CAR) which can be used to evaluate HPA-axis function further.
DUTCH Cycle Mapping, Sex Hormone Metabolism and Adrenal Metabolism by Precision Analytical
DUTCH Cycle Mapping, Sex Hormone Metabolism and Adrenal Metabolism are also available as standalone tests.
Micronutrients
Essential Vitamin Profile by Lab4More
Low levels of iron, calcium vitamin D, B12 and folic acid have been found in osteoporosis. This test can help you devise your micronutrient supplement plan.
- Zinc
- Vitamin E
- Vitamin D
- Vitamin B6
- Vitamin B2
- Vitamin B12
- Selenium
- Potassium
- Magnesium
- Iron
- Folic Acid
- Calcium
The Gut Microbiome
GI360 Complete with Add on H.Pylori by Doctor’s Data
Digestion and absorption issues are implicated in osteoporosis. Comprehensive Stool Analysis with PCR+ Parasitology, which includes various smaller panels for retesting specific areas of concern.
Heavy Metals
Mercury Tri Test by Quicksilver Scientific
Assesses the body’s mercury overall burden and ability to detoxify and eliminate mercury.
Blood Metals Panel by Quicksilver Scientific
Screens for eight nutrient elements and seven toxic metals for indication of elevated exposure to toxic metals or imbalances of nutrient elements in whole blood.
References
Aibar-Almazán, A., Voltes-Martínez, A., Castellote-Caballero, Y., Afanador-Restrepo, D. F., Carcelén-Fraile, M. del, & López-Ruiz, E. (2022). Current status of the diagnosis and management of osteoporosis. International Journal of Molecular Sciences, 23(16), 9465.
Feldman, M., Cryer, B., McArthur, K. E., Huet, B. A., & Lee, E. (1996). Effects of aging and gastritis on gastric acid and pepsin secretion in humans: A prospective study. Gastroenterology, 110(4), 1043–1052.
SIGN. (2020). Management of osteoporosis and the prevention of fragility fractures. Scottish Intercollegiate Guidelines Network. SIGN 142.