Michele Zini Servizio di Endocrinologia - Arcispedale S. Maria Nuova, IRCCS Reggio Emilia michele.zini@asmn.re.it

1. L'IPERTIROIDISMO SUBCLINICO è un FATTORE
DI RISCHIO per FRATTURA ?
Michele Zini
Unità Operativa di Endocrinologia
Arcispedale S. Maria Nuova IRCCS, Reggio Emilia
Michele.zini@asmn.re.it
Daniela Di Sarra
U.O.C. di Endocrinologia e Metabolismo
Dipartimento di Medicina - Azienda Ospedaliera Universitaria Integrata, Verona

2. Ipertiroidismo subclinico e depauperamento osseo
Faber J et al., European Journal of Endocrinology (1994) 130: 350–356
Meta-analysis including 15 studies
441 pre- and 317 post-menopausal women
taking thyroxine - TSH reduced in 92% of patients
Pre-menopausal women:
excess annual loss of 0.31% after 8.51 years
of l-T4 treatment as compared to healthy
premenopausal women (NS)
Post-menopausal women:
excess annual loss of 0.91% after 9.93 years
of l-T4 treatment as compared to healthy
postmenopausal women (P < 0.007)

3. Ipertiroidismo subclinico e depauperamento osseo
Faber 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.

4. Ipertiroidismo subclinico e depauperamento osseo
Uzzan B et al., Clin Endocrinol Metab. 1996 Dec;81(12):4278-89.
Meta-analysis including 41 studies
1250 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

5. [LoE ]
QUS and DEXA in patients with subclinical
hyperthyroidism
Tauchmanovà L et al., Maturitas 48 (2004) 299–306

6. [LoE ]
QUS and DEXA in patients with subclinical
hyperthyroidism
Tauchmanovà L et al., Maturitas 48 (2004) 299–306

7. [LoE ]
QUS and DEXA in patients with subclinical
hyperthyroidism
Tauchmanovà L et al., Maturitas 48 (2004) 299–306
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

8. Low TSH and bone status – NHANES III
Morris MS et al., Bone 40 (2007) 1128–1134
[LoE ]

9. Low TSH and bone status – NHANES III
Morris 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

10. Low TSH and bone status - The Tromsø Study
Grimnes 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.

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

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

13. Low TSH and bone status – the HUNT 2 study
Svare A et al., European Journal of Endocrinology (2009) 161 779–786
In conclusion, subnormal TSH
was associated with a decreased
BMD, especially prominent in the
TSH < 0.10 mU/l group.
[LoE ]

14. Effects of Levothyroxine on Bone Mineral Density
Schneider R et al., J Clin Endocrinol Metab 97: 3926–3934, 2012
[LoE ]
Women were
premenopausal

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

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

17. Normalization of TSH and bone loss
Faber J et al., Clin Endocrinol 48: 285-290, 1998
[LoE ]

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

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

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

21. Risk for Fracture in Women with Low TSH levels
Bauer 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

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

23. Incident Hip Fracture in Older Adults
Lee 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.

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

25. Fractures in
subclinical
hyperthyroidism:
The TEARS Study
Vadiveloo T et al.,
J Clin Endocrinol Metab 96:
1344–1351, 2011
[LoE ]

26. Subclinical thyroid disease
Surks MI, JAMA 291: 228-238, 2004

27. The skeletal consequences of thyrotoxicosis
Nicholls 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.

28. SUBCLINICAL HYPERTHYROIDISM:
TO TREAT OR NOT TO TREAT ?
An ongoing debate

29. ATA – AACE guideline
Bahn RS et al, Thyroid 21: 593-646, 2011