Methods for Assessing Bone Quality

Bone mass, geometry, and tissue material properties contribute to bone structural integrity. Thus, bone strength arises from both bone quantity and quality. Bone quality encompasses the geometric and material factors that contribute to fracture resistance. Although no single method can completely characterize bone quality, current noninvasive imaging techniques can be combined with ex vivo mechanical and compositional techniques to provide a comprehensive understanding of bone quality.

Methods for assessing mechanical properties include whole-bone, bulk tissue, microbeam, and micro- and nanoindentation testing techniques. Outcomes include structural strength and material modulus. Advantages include direct assessment of bone strength; disadvantages include specimen destruction during testing.

 Methods for characterizing bone geometry and microarchitecture include quantitative CT, high-resolution peripheral quantitative CT, high-resolution MRI, and micro-CT. Outcomes include three-dimensional whole-bone geometry, trabecular morphology, and tissue mineral density. The primary advantage is the ability to image noninvasively; disadvantages include the lack of a direct measure of bone strength.

 Methods for measuring tissue composition include scanning electron microscopy, vibrational spectroscopy, nuclear magnetic resonance imaging, and chemical and physical analytical techniques. Outcomes include mineral density and crystallinity, elemental composition, and collagen crosslink composition. Advantages include the detailed material characterization; disadvantages include the need for a biopsy.

Clinical Orthopaedics and Related Research, Volume 469, Number 8 (2011), 2128-2138.

Is Strontium Ranelate Safe?

“Clinical trials are designed to assess efficacy, not safety and so post marketing data is needed to evaluate safety. Jakob et al report the results of an observational cohort study to assess safety and treatment persistence with SR during 3 years follow-up in 12,702 postmenopausal women from 7 countries (29). Mean age was 69.0 years with 16.5% of patients being over 80 years. Mean follow-up duration was 32 months and mean treatment duration was 25.2 months (24,956 patient-years of treatment). VTE was reported in 55 patients, an incidence of 2.1/1000 patient-years (95% CI 1.6, 2.8), lower than that observed in patients treated with SR in the phase III studies (7.9/1000 patient-years; 95% CI 6.3, 9.7). No DRESS syndrome or Stevens-Johnson syndrome was reported. Persistence of SR treatment was 80%, 68% and 64% after 12, 24 and 32 months treatment, respectively.”

29. Jakob FJ, Palacios S, Audran M, et al. Final results of a 3 years prospective observational cohort study of patients treated with strontium ranelate. Osteoporos Int 2012;23(Suppl 2):S73.

http://www.iofbonehealth.org/volume-12-issue-2

Vitamins B6 and B12 and Folic Acid

Readers of my blog know that I advocate taking strontium citrate along with a combination of vitamins, minerals, and other supplements for bone health. Most people understand that calcium, magnesium, and vitamin D are essential for strong bones. Some people are adding vitamin K1 and/or vitamin K2 (MK4 or MK7) to their supplement lists. But did you know that you may also need vitamins B6 and B12 and folic acid?

“Some studies suggest high blood levels of the amino acid homocysteine may be linked to lower bone density and higher risk of hip fracture in the elderly. Vitamins B6 and B12, as well as folic acid, play a role in changing homocysteine into other amino acids for use by the body; so, it is possible that they might play a protective role in osteoporosis. Research is ongoing as to whether supplementation with these B vitamins might reduce fracture risk.” This paragraph is quoted from:
http://www.iofbonehealth.org/nutrition

The studies referred to are:

1. McLean RR, Jacques PF, Selhub J, et al. (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350:2042-49
2. Morris MS, Jacques PF, Selhub J (2005) Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 37:234-42

I take Nature's Bounty Sublingual Vitamin B12, 5000 mcg (5 mg) per microlozenge. I was using it three times per week, but I have recently increased my intake to the recommended dosage of one microlozenge daily. You dissolve these under your tongue for maximum absorption.

My multivitamin, Nature Made Multi For Her 50+, contains 6 mg of vitamin B6,25 mcg of vitamin B12, and 400 mcg of folic acid.

Effects of Strontium Citrate on Osteoblasts

The objective of this study was to assess the effects of strontium citrate on the proliferation and differentiation of osteoblastic cells obtained from human alveolar bone. Primary osteoblasts, obtained from human alveolar bone residues at the time of third molar extractions and explanted in culture, were seeded in BGJb media containing 10% FCS. After the cells reached a semiconfluent stage, strontium citrate (bibasic anhydrous, pure grade from Jost Chemical) at various concentrations (0.05-1.0 mM) was added.

The MTT test showed the cells to be responsive to strontium citrate with significant increases in cellular activity/proliferation at 24 and 48 hrs. Alkaline phosphatase activity was significantly enhanced at 48 and 72 hrs with strontium citrate concentrations in the test range.

The data support the hypothesis that strontium citrate increases the proliferative/alkaline phosphatase activity of human osteoblastic cells from alveolar bone. The results validate previous research that has been done with other forms of strontium in clinical studies and rodent calvarial cells and indicates that strontium citrate could be a promising agent in treating oral as well as systemic bone disorders.

http://iadr.confex.com/iadr/2007orleans/techprogram/abstract_89231.htm

Interpretation of BMD Scans in Patients Stopping Strontium Ranelate Treatment

“The oral administration of strontium ranelate causes a clinically significant overestimation of BMD because of the high attenuation of X-rays by strontium atoms in bone." GM Blake and I. Fogelman “performed a theoretical study to calculate the long-term effect of strontium treatment on BMD and establish the duration of past treatment for which the remaining bone strontium content (BSC) has a negligible effect on BMD.” “Estimates of the strontium BMD artefact after treatment has stopped were performed on the assumption that the BSC effect accounts for 75% of the total measured BMD change at 3 years.” “If 75% of the BMD changes are explained by BSC, in the average patient, 3-year treatment leads to a spine BMD artefact of 11.2%, decreasing to 3.8% 10 years after stopping treatment. The BMD artefacts at the total hip and femoral neck sites are smaller by factors of 0.65 and 0.53, respectively.” “On average, 6-month treatment is required for the spine BMD artefact to exceed 3%, the figure adopted as the maximum BMD change caused by bone strontium that has a negligible effect on scan interpretation.” The researchers concluded that “strontium ranelate treatment lasting for > 6 months can affect BMD measurements for many years afterward.” http://www.ncbi.nlm.nih.gov/pubmed/16939400 J Bone Miner Res. 2006 Sep;21(9):1417-24.

Minimum Effective Doses of Strontium

The aim of the PREVOS study (PREVention Of early postmenopausal bone loss by Strontium ranelate) and the STRATOS study (STRontium Administration for Treatment of OSteoporosis) was to determine the minimum dose at which strontium ranelate (SR) is effective in, respectively, the prevention of bone loss in early postmenopausal nonosteoporotic women and the treatment of postmenopausal vertebral osteoporosis.

The minimum dose at which SR is effective in preventing bone loss in early postmenopausal nonosteoporotic women and in the treatment of postmenopausal osteoporosis is 1 g/day and 2 g/day, respectively.

Strontium ranelate phase 2 dose-ranging studies: PREVOS and STRATOS studies, J. Y. Reginster and P. J. Meunier, Osteoporosis International, Volume 14, Supplement 3, 56-65, DOI: 10.1007/s00198-002-1349-0

The chemical structure of strontium ranelate is composed of two atoms of stable strontium combined with organic ranelic acid. Strontium is the bone active component and makes up 34% by weight of the whole molecule, so each 2 g dose of strontium ranelate delivers 680 mg of elemental strontium.

 Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review of safety and efficacy, Glen M Blake and Ignac Fogelman, Clinical Interventions in Aging, Dec. 2006, 1(4): 367-375

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699648/