Associations between osteoporosis and drug exposure: a post-marketing study of the World Health Organization pharmacovigilance database

[helvella]

This is a comprehensive paper on the impact of medicines on bone density, osteoporosis and fracture.

Thyroid hormones are listed but their impact appears considerably lower than for Proton Pump Inhibitors (PPIs), Methotrexate, Steroids, Hydroxychloroquine, and others.

It is also often mentioned here that some people found their BMD improved due to adequate thyroid hormone treatment. It is difficult to separate out the effects of inadequate thyroid hormone, excess thyroid hormone (whether exogenous or endogenous) and optimal thyroid hormone, especially when we consider liothyronine (T3) as well as levothyroxine (T4). Obviously, if patients' BMD levels have fallen due to hypothyroidism, a simplistic check could appear to suggest that those on thyroid hormone have worse BMD and imply causality.

Bone. 2021 Jul 31;116137.

doi: 10.1016/j.bone.2021.116137. Online ahead of print.

Associations between osteoporosis and drug exposure: a post-marketing study of the World Health Organization pharmacovigilance database (VigiBase®)

Benjamin Batteux 1 , Youssef Bennis 2 , Sandra Bodeau 2 , Kamel Masmoudi 3 , Anne-Sophie Hurtel-Lemaire 3 , Said Kamel 4 , Valérie Gras-Champel 2 , Sophie Liabeuf 2

Affiliations

• PMID: 34343739

• DOI: 10.1016/j.bone.2021.116137

Highlights

What is already known about the subject?

• Several drugs are known to induce osteoporosis and/or increase the fracture risk.

• Pharmacovigilance and pharmacoepidemiologic studies are crucial for the safety assessment of marketed drugs.

What this study adds?

• New disproportionality signals with a pharmacologically plausible mechanism in bone fragility were found for drugs used in the fields of neurology (selective 5-HT1 agonists, levodopa and memantine), hematology (romiplostim), pulmonology (macitentan), ophthalmology (ranibizumab), and rheumatology (tofacitinib).

Abstract

Background: Bone remodeling is a complex process, and many conditions (including drug exposure) lead to osteoporosis. Here, we sought to detect new disproportionality signals for drugs associated with osteoporosis.

Methods: We performed a disproportionality analysis of the World Health Organization's VigiBase® pharmacovigilance database through April 12, 2020. The frequency of reports on osteoporosis for all identified drug classes was compared with that for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)].

Results: Of the 7,594,968 cases spontaneously recorded to VigiBase®, 4,758 concerned osteoporosis. New disproportionality signals with a pharmacologically plausible mechanism were found for drugs used in neurology (levodopa (ROR [95%CI]: 10.18 [4.33-25.10]), selective serotonin agonists (4.22 [2.34-7.00]) and memantine (4.10 [1.56-8.93])), hematology (romiplostim (4.93 [1.15-21.10])), pulmonology (macitentan (3.02 [1.84-4.90])), ophthalmology (ranibizumab (3.31 [1.00-10.51])) and rheumatology (tofacitinib (3.65 [3.00-4.40])). The robustness of these new results is supported by the significant RORs for the vast majority of drugs already known to induce osteoporosis and/or increase the fracture risk, namely glucocorticoids, gonadotropin-releasing hormone analogs, anti-aromatases, androgen receptor blockers, thyroid hormones, proton pump inhibitors, thiazolidinediones, vitamin K antagonists, loop diuretics, protease inhibitors, nucleoside and nucleotide reverse transcriptase inhibitors, and enzyme-inducing antiepileptics including barbiturates and derivatives, hydantoin derivatives, carboxamide derivatives and fatty acid derivatives.

Conclusion: We established up a comprehensive list of drugs potentially associated with osteoporosis and highlighted those with pharmacologically plausible mechanisms leading to bone fragility. Our results might pave the way for additional exploration of these mechanisms.

Keywords: Drug; Osteoporosis; Pharmacoepidemiology; Pharmacology; Pharmacovigilance.

pubmed.ncbi.nlm.nih.gov/343...

Currently full paper is accessible from the following link but this might change when the paper is finalised.

sciencedirect.com/science/a...

[TSH110]

Very interesting - thanks for posting

[diogenes Remembering]

I looked at the conclusions from a paper cited in this report:

Effect of postoperative thyrotropin suppressive therapy on bone mineral density in patients with papillary thyroid carcinoma: A prospective controlled study

Wao Sugitani MD, PhD Yoshihide Fujimoto MD, PhD

doi.org/10.1016/j.surg.2011...

This paper purports to show that TSH suppression in patients after thyroid cancer removal, by T4 or combination, gives a greater frequency of OP in those over 50 but no extra danger when less than 50. In the older group it seems that 20 patients suffered bone density loss after 1 year and 100 didn't. Even those with no suppression still suffered some OP after 5 years. But these studies make one general error. They look at statistical results over a group of patients and include all individuals in the outcome . This means that patients who WOULD suffer OP are a different group than those who didn't but they are all considered together. TSH suppression may well be a warning for some patients, but it can't be simply extended to all. The response to suppressed TSH and the OP outcome is therefore variable and individual and can't really be prospectively levelled at the individual patient.

[Tythrop]

Obviously its not possible to create a "suffering score" ir league tabke, but it can't be denied that hypothyroidism causes suffering in the same way as osteoporosis. Which causes the most suffering is probably subjective. But surely to deny adequate thyroid therapy because it might cause osteoparosis cant be right in my view.