Pekka Mäkelä

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens.

The effect of clodronate on bone mineral density (BMD) was studied in 121 post-menopausal breast cancer women without skeletal metastases. In addition, two antioestrogens, tamoxifen and toremifene, were compared in their action on bone mineral density. Patients were randomized to have an adjuvant antioestrogen treatment either 20 mg of tamoxifen or 60 mg of toremifene daily for 3 years. In addition all patients were randomized to have 1600 mg of oral clodronate daily or to act as control subjects. BMD of the lumbar spine and femoral neck were measured by dual-energy radiographic absorptiometry before therapy and at 1 and 2 years. At 2 years, clodronate with antioestrogens markedly increased BMD in the lumbar spine and femoral neck by 2.9% and 3.7% (P = 0.001 and 0.006 respectively). There were no significant changes in BMD in the patients given antioestrogens only. No significant differences were found between tamoxifen and toremifene on bone mineral density. Clodronate with antioestrogens significantly increased bone mass in the lumbar spine and femoral neck. Both antioestrogens, tamoxifen and toremifene, similarly prevented bone loss in the lumbar spine and femoral neck.

Transdermal oestrogen therapy protects postmenopausal liver transplant women from osteoporosis. A 2-year follow-up study

BACKGROUND/AIMS Hormone replacement therapy (HRT) prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the benefits of oestrogen therapy in liver transplant patients have not been studied. METHODS The effect of transdermal HRT was studied in 33 postmenopausal liver transplant women. The main outcome measure was the change in bone mineral density (BMD) which was measured annually for 2 years. The effect on bone turnover was studied by assessment of the serum aminoterminal propeptide of type I procollagen (PINP). RESULTS The mean lumbar BMD increased from 0.816 at baseline to 0.858 and to 0.878 g/cm2 (P < 0.001) after 1 and 2 years of therapy, respectively. The BMD of the femoral neck increased from 0.665 to 0.690 g/cm2 (P < 0.006). During the first and second years, the mean BMD of the lumbar spine increased by 5.3 and 1.2%, while that of the femoral neck increased by 3.3 and 1.2%. After 2 years of HRT, only one-fifth of the patients had osteoporosis, whereas over half of the women had osteoporosis at baseline. The median serum PINP decreased by 47% at 1 year and remained decreased at 2 years compared with baseline levels. CONCLUSION Transdermal HRT decreased the turnover rate of mineralized bone matrix. Transplant women responded with increased BMD, just like healthy postmenopausal women.

The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer

In this study we report bone mineral density (BMD) changes during clodronate and antioestrogen treatment in women with breast cancer having discontinued hormone replacement therapy (HRT) at the time of operation compared to women who had not used HRT immediately before the operation. 61 postmenopausal women with operable breast cancer were treated with the adjuvant antioestrogen tamoxifen 20 mg or toremifene 60 mg daily for 3 years. All patients were randomized to clodronate (1.6 g daily orally) or control groups for 3 years. 23 patients had recently (recent users) and 38 never or not for at least 1 year before operation used HRT (non-users). BMD of lumbar spine and femoral neck were measured before antiresorptive therapy (antioestrogens and clodronate) and at 1, 2, 3 and 5 years thereafter. All patients were disease-free at the time of BMD measurements. Patients who had recently used HRT had more significant bone loss as compared to HRT non-users at 3 years in lumbar spine – 3.0% vs. + 1.2% (P< 0.001), but not in femoral neck – 0.4% vs. + 1.7% (P = 0.27). Adding 3-year clodronate treatment to antioestrogen therapy improved BMD marginally at 3 years: lumbar spine + 1.0% vs. –1.7% (P = 0.01) and femoral neck + 2.4% vs. –0.4% (P = 0.12). This was also seen at 5 years of follow-up, 2 years after termination of the antiresorptive therapy: HRT recent users vs. HRT non-users in lumbar spine –6.5% vs. +0.5% (P< 0.0001) and in femoral neck –4.8% vs. –1.5% (P = 0.38); and clodronate vs. controls in lumbar spine –1.0% vs. –3.2% (P = 0.06) and in femoral neck –0.1% vs. –5.2% (P = 0.001, respectively). The type of endocrine therapy (tamoxifen and toremifene) had no significant influence on BMD changes. We conclude from this study that postmenopausal women who have recently discontinued HRT experience more rapid bone loss than HRT non-users. Neither 3-year antioestrogen therapy alone nor antioestrogen together with clodronate could totally prevent the bone loss related to HRT withdrawal in lumbar spine, even though clodronate seemed to retard it.

A realist account of the ontology of impairment

This paper provides a philosophical analysis of the ontology of impairment, in part social and in part not. The analysis is based on the division between two categories of facts concerning the world we live in: “brute” and institutional facts. Brute facts are those that require no human institution for their existence. To state a brute fact requires naturally the institution of language, but the fact stated is not the same as the statement of it. For example, regardless of any human institution or opinion, the presence of an extra chromosome 21 is a brute fact, and despite of people’s constructions or deconstructions, this fact remains. As for the lives of people with extra chromosome 21, the social reality and human institutions enter the picture. The social and moral status of these people is never a matter of brute fact.

Ultrasonography of the axilla in the follow-up of breast cancer patients who have a negative sentinel node biopsy and who avoid axillary clearance

The clinical value of ultrasonography of the axilla in detection of breast cancer recurrence is not known among patients who have a negative sentinel node biopsy and avoid axillary clearance. We studied a cohort of 205 such patients using ultrasonography one and three years after breast surgery. A recurrent tumour was found in the axilla in only two (0.5%) of the total of 383 ultrasound examinations performed during the study, and only one (0.3%) of the 369 examinations performed at the scheduled study visits revealed cancer. None of the ultrasound examinations was false positive, and no study participant was subjected to unnecessary surgery due to ultrasound monitoring. We conclude that the rate of breast cancer recurrence in the ipsilateral axilla is low following sparing of the axillary contents, and that monitoring of such patients with repeated ultrasound examinations is unlikely to be cost-effective.

Understanding Institutions without Collective Acceptance

Francesco Guala has written an important book proposing a new account of social institutions and criticizing existing ones. We focus on Guala’s critique of collective acceptance theories of institutions, widely discussed in the literature of collective intentionality. Guala argues that at least some of the collective acceptance theories commit their proponents to antinaturalist methodology of social science. What is at stake here is what kind of philosophizing is relevant for the social sciences. We argue that a Searlean version of collective acceptance theory can be defended against Guala’s critique and question the sufficiency of Guala’s account of the ontology of the social world.

Raimo Tuomela: Response to Raul Hakli and Pekka Mäkelä

In their paper Hakli and Makela propose an account of we-mode planning in view of the fact that my theory needs one. There is rather little on planning in my 2013 social ontology book (SO), although in some earlier work I have touched on the topic in some more detail.1 These authors claim that planning is an important topic needed for a philosophical theory of collective and group action. I agree that a comprehensive account of we-mode planning would be a desirable addition to the theory.

Planning in the We-mode

In philosophical action theory there is a wide agreement that intentions, often understood in terms of plans, play a major role in the deliberation of rational agents. Planning accounts of rational agency challenge game- and decision-theoretical accounts in that they allow for rationality of actions that do not necessarily maximize expected utility but instead aim at satisfying long-term goals. Another challenge for game-theoretical understanding of rational agency has recently been put forth by the theory of team reasoning in which the agents select their actions by doing their parts in the collective action that is best for the group. Both planning and team reasoning can be seen as instances of a similar type of reasoning in which actions are selected on the basis of an evaluation of a larger unit than an individual’s momentary act. In recent theories of collective agency, both planning and team reasoning have been defended against orthodox game theory, but, interestingly, by different authors: Raimo Tuomela has defended team reasoning in his theory of group agency, but he ignores temporally extended planning in this context. Michael Bratman has extended his theory of planning to the case of shared agency, but he does not seem to see a role for team reasoning in understanding shared intentional activities. In this paper, we argue that both accounts suffer from this one-sidedness. We aim to combine the main insights of Tuomela’s we-mode approach and Bratman’s planning approach into a fruitful synthesis that we think is necessary for understanding the nature of group agency.

Others Will Do It: Social Reality by Opportunists

Raimo Tuomela is known to be a philosopher who enjoys criticism more than applause. This fact in our minds we have decided to write a critical paper to further stimulate philosophical discussion in the field of social ontology. We want to examine the role of we-attitudes in the existing philosophical analyses of social reality. It is our view that we-attitudes have gained too central a place in the leading philosophical accounts of social ontology. (Searle 1995; Tuomela 1995, Tuomela & Balzer 1999) We acknowledge the importance of we-attitudes, but think their role in the analysis of social institutions has been exaggerated.