Ipertiroidismo e fratture

L'IPERTIROIDISMO SUBCLINICO è un FATTORE DI RISCHIO per FRATTURA ?

Michele ZiniUnità Operativa di EndocrinologiaArcispedale S. Maria Nuova IRCCS, Reggio Emilia

[email protected]

Daniela Di SarraU.O.C. di Endocrinologia e Metabolismo Dipartimento di Medicina - Azienda Ospedaliera Universitaria Integrata, Verona

Ipertiroidismo subclinico e depauperamento osseoFaber J et al., European Journal of Endocrinology (1994) 130: 350–356

Meta-analysis including 15 studies441 pre- and 317 post-menopausal womentaking thyroxine - TSH reduced in 92% of patients

Pre-menopausal women:excess annual loss of 0.31% after 8.51 yearsof l-T4 treatment as compared to healthy

premenopausal women (NS)

Post-menopausal women:excess annual loss of 0.91% after 9.93 yearsof l-T4 treatment as compared to healthy

postmenopausal women (P < 0.007)

Ipertiroidismo subclinico e depauperamento osseoFaber J et al., European Journal of Endocrinology (1994) 130: 350–356

In conclusion, the meta-analysis on the available crosssectional studies:

a) did not find any significant reduction in bone mass during prolonged l-T4 treatment resulting in reduced serum TSH in premenopausal women.

b) in contrast, l-T4 treatment in postmenopausal women in a dosis leading to reduced serum TSH resulted in a significant excess of annual bone loss in comparison to control women.

Ipertiroidismo subclinico e depauperamento osseoUzzan B et al., Clin Endocrinol Metab. 1996 Dec;81(12):4278-89.

Meta-analysis including 41 studies1250 patients taking thyroxine

For lumbar spine and hip (as for all other sites), suppressive TH therapy was associated with significant bone loss in postmenopausal women (but not in premenopausal women)

The detrimental effect of TH appeared more marked on cortical bone than on trabecular bone

QUS and DEXA in patients with subclinical hyperthyroidism Tauchmanovà L et al., Maturitas 48 (2004) 299–306

[LoE ]


[LoE ]


[LoE ]

Conclusions:

• A significant increase in bone turnover markers and a decrease in bone mass was found in women affected by endogenous subclinical hyperthyroidism

• It is greater in early postmenopausal patients

• Cortical rich bone was mainly affected

• Both QUS and the conventional DEXA technique were equally able to determine bone density decrease

Low TSH and bone status – NHANES IIIMorris MS et al., Bone 40 (2007) 1128–1134 [LoE ]

Low TSH and bone status – NHANES IIIMorris MS et al., Bone 40 (2007) 1128–1134 [LoE ]

In conclusion, we found:

• associations between low-normal serum TSH and osteopenia and osteoporosis

• a graded increase in BMD with increasing serum TSH across the normal range

Low TSH and bone status - The Tromsø StudyGrimnes G et al., Thyroid 18: 1147-1155, 2008. [LoE ]

• Postmenopausal women with low serum TSH had significantly lower BMD at the distal and ultradistal forearm sites compared to women with serum TSH in the 2.5–97.5 percentile range

• The same was found in men at the ultradistal forearm site.

Low TSH and bone status – the HUNT 2 studySvare A et al., European Journal of Endocrinology (2009) 161 779–786 [LoE ]



In conclusion, subnormal TSH was associated with a decreased BMD, especially prominent in the TSH < 0.10 mU/l group.

Effects of Levothyroxine on Bone Mineral DensitySchneider R et al., J Clin Endocrinol Metab 97: 3926–3934, 2012 [LoE ]

Women were premenopausal



Conclusions:There was little evidence of adverse LT4 effects on bone;however, premenopausal women with DTC might be at risk for reduced vBMD in their ultradistal radii.

Normalization of TSH and bone lossFaber J et al., Clin Endocrinol 48: 285-290, 1998 [LoE ]

Risk for Fracture in Women with Low TSH levelsBauer DC et al., Ann Intern Med. 2001;134:561-568. [LoE ]




In conclusion, we found that:• older women with biochemical evidence of

excess thyroid hormone have an increased risk for hip and vertebral fractures

• no evidence exists that thyroid hormone use itself adversely effects fracture rates if TSH levels are normal

• previous hyperthyroidism is independently associated with an increased risk for hip fracture

Incident Hip Fracture in Older AdultsLee JS et al., Arch Intern Med. 2010;170(21):1876-1883 [LoE ]

Incident Hip Fracture in Older AdultsLee JS et al., Arch Intern Med. 2010;170(21):1876-1883 [LoE ]

Conclusions:

Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture.

Whether treatment of the subclinical syndrome reduces this risk is unknown.

Fractures in subclinical hyperthyroidism - TEARS StudyVadiveloo T et al., J Clin Endocrinol Metab 96: 1344–1351, 2011 [LoE ]

Fractures in subclinical hyperthyroidism:The TEARS Study

Vadiveloo T et al.,J Clin Endocrinol Metab 96: 1344–1351, 2011

[LoE ]

Subclinical thyroid diseaseSurks MI, JAMA 291: 228-238, 2004

The skeletal consequences of thyrotoxicosisNicholls JJ et al., Journal of Endocrinology (2012) 213, 209–221

In summary, endogenous subclinical hyperthyroidism may be associated with:

• an increased bone turnover• reduced BMD• increased fracture risk in

• postmenopausal women• men• but not in pre-menopausal women

although insufficient data are currently available to draw definitive conclusions.

SUBCLINICAL HYPERTHYROIDISM:TO TREAT OR NOT TO TREAT ?

An ongoing debate

ATA – AACE guidelineBahn RS et al, Thyroid 21: 593-646, 2011

Ipertiroidismo e fratture

Health & Medicine