A review of the medical and scientific literature was undertaken to identify micronutrient elements associated with bone health status [16
] by assessing available medical and scientific literature from MEDLINE/PubMed, as well as by reviewing numerous books, nutrition journals, and health periodicals, conference proceedings, and government publications. References cited in identified publications were also examined for additional relevant writings. The evidence base to support the role of specific essential micronutrients in bone status ranges from scant to very firm, depending on the compound [18
]. Multiple studies have demonstrated that micronutrients (and drugs derived from nutrients) beyond just calcium and vitamin D have an impact on bone health. Vitamin K2
], strontium [16
], magnesium [26
], and DHA [27
] have all been implicated in improving the status of bones, but to our knowledge, none of these individual micronutrients have been assessed when given in combination.
The first author practices environmental medicine, where many referred patients present with long-term chronic disease. With the view that comprehensive fracture risk assessment should be a routine part of patient care, and the observation that patients with chronic disease have higher rates of bone compromise and frequently do not receive therapy to prevent fractures [31
], bone health determination was established as a component of the overall clinical assessment in chronically ill patients. Starting in 2006, patients found to have suboptimal BMDs were provided with options for management, including micronutrient therapy. As well as discussion related to lifestyle and standard-of-care pharmaceutical interventions, the potential consequences of not intervening, and the scientific literature on the published efficacy of micronutrient interventions were presented to patients along with information on recommended clinical practice guidelines for compromised bone health.
Some patients adamantly refused to use pharmaceutical therapies while others reported they had previously discontinued such therapy because of continued loss of BMD. A portion of these individuals indicated interest in supplemental nutrients linked in the scientific literature to improved bone health status. As patients presenting to environmental health specialists often have chemical sensitivities [34
], the reluctance expressed to using pharmaceuticals was sometimes related to a sensitivity to medications or excipients commonly used within dispensed drugs.
Patients wishing to explore micronutrient use were given medical literature detailing the benefits purported in various studies. Eager to ameliorate their bone health status if possible, some individuals chose to use micronutrients rather than using pharmacologic therapies or not using any intervention at all. After 12 months of consecutive micronutrient therapy, repeat BMDs were performed to assess for evidence of change. A retrospective review of the outcomes was undertaken to gather data for analysis.
2.1. Demographics and Inclusion Criteria
The population of patients for the study came from an environmental medicine clinic in Edmonton, Alberta, Canada. Out of 219 patients assessed, 16 were still in the process of taking supplements (data not yet complete) and 126 were excluded. Exclusion criteria included patients with recognized bone compromising medical conditions or those on medications known to potentially affect bone health. (e.g., 1 with anorexia nervosa and 1 on chemotherapy) as well as patients who had repeat BMD measurements inadvertently performed on different machines from the original (5 patients)—making comparison inaccurate. In addition, 37 patients were excluded because they did not comply with therapy (the micronutrients were taken inconsistently—self-reported at less than half the time), 6 patients commencing the protocol changed their mind about taking the nutrients (for financial reasons), and 71 patients did not return at the end of the time period for follow-up BMD assessment or decided they did not want a repeat BMD and therefore had incomplete data. Two patients died during the course of the study, unrelated to the intervention (1 from ALS and the other from a motor vehicle accident). The final sample of 77 patients taking the micronutrient combination most or all of the time was included with complete data for analysis. shows the demographics for the study group.
Distribution of bone density diagnosis in the sample.
2.2. Protocol and Rationale
Each patient in the analysis who chose to use the micronutrient intervention followed a suggested daily protocol of supplemental nutrient consumption and exercise as described in . It was hypothesized that perhaps bone compromise might be related to nutritional insufficiency in some patients and that remediation of nutritional biochemistry may be of assistance in restoring bone health. Also, both DHA and vitamin D are involved in genetic regulation of many genes and restoration of optimal levels has been associated with improved bone strength [35
]. Given the debate about the efficacy of calcium supplementation for reducing fractures [39
] and the potential risks associated with high-dose supplementation including renal calculi and cardiovascular events [40
], patients were advised to obtain calcium from dietary sources including vegetables such as Brussels sprouts or broccoli rather than calcium supplements. Patients were also instructed to commence and maintain a regimen of daily impact exercises such as jumping jacks or skipping where possible as impact has been associated with prevention of bone density loss [42
Combination of micronutrients (COMB) Protocol for Bone Health.
As BMD is a major determinant among several risk factors for predicting fragility fractures, BMD follow-up measurement was therefore used as an intervention outcome along with fall surveillance. The main areas analyzed for bone density included the lumbar spine, the femoral neck, and the femoral trochanter. In this study, we evaluated comparative differences in the femoral neck, total hip, and total spine in relation to previous studies. We also investigated change at the lowest hip and lowest spine sites to determine whether there was improvement in the areas that were the least dense and potentially the most vulnerable.
Statistics were calculated with SPSS 18.0 (IBM Corporation, USA). Pre- and postintervention bone densities were compared using a one-way ANOVA with a P value threshold of 0.05. Changes were also evaluated using mean percentage change over one year to compare treatment effect with the bisphosphonates and strontium ranelate. In the analyses, z-scores were used in order to avoid any age-related bias in some other BMD scores.
In addition, a post hoc analysis of the noncompliant group (N = 37) was carried out to evaluate whether adherence to the combined micronutrient strategy was beneficial. One-way ANOVA with a P value threshold of 0.05 was again used to determine if this group showed a significant difference over the course of the one year period. Moreover, the percentage change at each site in this group was compared to the percentage change in the intervention group.
Nineteen patients (25%) were classified in the normal category despite having low bone mass or suboptimal levels when age-matched to general population standards. According to the interpretation of the reports provided, the “bone quality in younger individuals differs from that of older people” and thus “absolute fracture risk has not been determined in this population.” As such, diminished bone health with levels considerably lower than the mean are still placed in a “normal” diagnostic category. BMD testing was done on various younger patients as many of these individuals presented with chronic illness and had evidence of irregularities on biochemical nutritional status testing, or had other factors that might predispose them to bone health compromise.